Роль интерлейкина 1 в развитии заболеваний человека
https://doi.org/10.14412/1995-4484-2016-60-77
Аннотация
Иммуновоспалительные заболевания человека в зависимости от преобладающих механизмов активации иммунитета разделяются на две основные категории: аутоиммунные и аутовоспалительные. В то же время между аутоиммунными и аутовоспалительными заболеваниями много общего в отношении как спектра клинических проявлений, так и «триггерных» внешнесредовых, эпигенетических и генетических факторов, медиаторов воспаления, тканевого повреждения и подходов к фармакотерапии. Предполагается, что гиперпродукция «провоспалительного» цитокина – интерлейкина 1 (ИЛ1) – во многом определяет «перекрест» между аутоиммунитетом и аутовоспалением, характерный для многих иммуновоспалительных заболеваний. Изучение роли ИЛ1 в регуляции взаимодействия между врожденным (активация Toll-подобных рецепторов, инфламмасомы) и приобретенным (Th1- и Th17-типы иммунного ответа) иммунитетом и эффективности ингибиторов ИЛ1 может иметь важное значение в плане расшифровки патогенетических механизмов иммуно-воспалительных заболеваний человека и разработки новых подходов к персонифицированной терапии.
Об авторах
Е. Л. Насонов
ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой;
ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России
Россия
Россия
директор ФГБНУ НИИР им. В.А. Насоновой, академик РАН, докт. мед. наук, профессор,
115522 Москва, Каширское шоссе, 34А,
119991 Москва, ул. Трубецкая, 8, стр. 2
М. С. Елисеев
ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой
Россия
Россия
зав. лабораторией микрокристаллических артритов, канд. мед. наук,
115522 Москва, Каширское шоссе, 34А
Список литературы
1. McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med. 2006;3:e297. doi: 10.1371/journal.pmed.0030297
2. Doria A, Zen M, Bettio S, et al. Autoinflammation and autoimmunity: Bridging the divide. Autoimm Rev. 2012;12:22-30. doi: 10.1016/j.autrev.2012.07.018
3. Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity. 2013;39:1003-18. doi: 10.1016/j.immuni.2013.11.010
4. Dinarello CA. An expanding role for interleukin-1 blockade from gout to cancer. Mol Med. 2014 Dec 16;20 Suppl 1:S43-58. doi: 10.2119/molmed.2014.00232
5. Lopalco G, Cantarini L, Vitale A, et al. Interleukin-1 as common denominator from autoinflammatory to autoimmune disorders: premises, perils, and perspectives. Mediators Inflamm. 2015;2015:194864. doi: 10.1155/2015/194864
6. Насонов ЕЛ. Интерлейкин 1 и его роль в патологии человека. Терапевтический архив. 1987;(12):112-7 [Nasonov EL. Interleukin-1 and its role in human pathology. Terapevticheskii arkhiv. 1987;(12):112-7 (In Russ.)].
7. Schett G, Dayer J-M, Manger B. Interleukin-1 function and role in rheumatic disease. Nat Rev Rheumatol. 2016 Jan;12(1):14-24. doi: 10.1038/nrrheum.2016.166
8. Ильина АЕ, Станислав МЛ, Денисов ЛН, Насонов ЕЛ. Интерлейкин 1 как медиатор воспаления и терапевтическая мишень. Научно-практическая ревматология. 2011;49(5):62-71 [Il'ina AE, Stanislav ML, Denisov LN, Nasonov EL. Interleukin-1 as a mediator of inflammation and therapeutic target. Nauchnoprakticheskaya revmatologiya = Rheumatology Science and Practice. 2011;49(5):62-71 (In Russ.)]. doi: 10.14412/1995-4484-2011-1463
9. So A, Ives A, Joosten LAB, Busso N. Targeting inflammasomes in rheumatic diseases. Nat Rev Rheumatol. 2013;9:391-9. doi: 10.1038/nrrheum.2013.61
10. Dinarello CA, van der Meer JWM. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol. 2013;25:469-84. doi: 10.1016/j.smim.2013.10.008
11. Gabay G, Lamacchia C, Palme G. IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol. 2014;6:232-41. doi: 10.1038/nrrheum.2010.4
12. Sims JE, Smith DE. The IL-1 family: regulators of immunity. Nat Rev Immunol. 2010;10:89-102. doi: 10.1038/nri2691
13. Насонов ЕЛ, Денисов ЛН, Станислав МЛ. Интерлейкин 17 – новая мишень для антицитокиновой терапии иммуно-воспалительных ревматических заболеваний. Научно-практическая ревматология. 2013;51(5):545-52 [Nasonov EL, Denisov LN, Stanislav ML. Interleukin-17 is a new target for anti-cytokine therapy of immune inflammatory rheumatic diseases. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(5):545-52 (In Russ.)]. doi: 10.14412/1995-4484-2013-1547
14. Singh RP, Hasan S, Sharma S, et al. Th17 cells in inflammation and autoimmunity. Autoimmun Rev. 2014;13:1174-81. doi: 10.1016/j.autrev.2014.08.019
15. Spits H, Arti D, Colonna M, et al. Innate lymphoid cells – a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13:145-9. doi: 10.1038/nri3365
16. Jimenez-Dalmaroni MJ, Gerswhin ME, Adamopoulos IE. The critical role of toll-like receptors – from microbial recognition to autoimmunity: A comprehensive review. Autoimmun Rev. 2016;15:1-8. doi: 10.1016/j.autrev.2015.08.009
17. Afonina IS, Mü ller C, Martin SJ, Beyaert R. Proteolytic processing of Interleukin-1 family cytokines: variations on a common theme. Immunity. 2015;42:991-1004. doi: 10.1016/j.immuni.2015.06.003
18. Guo H, Callaway JB, Jenny P-Y, Ting JP-Y. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21:677-87. doi: 10.1038/nm.3893
19. Netea MG, van de Veerdonk FL, van der Meer JW, et al. Inflammasome-independent regulation of IL-1-family cytokines. Ann Rev Immunol. 2015;33:49-77. doi: 10.1146/annurevimmunol-032414-112306
20. Schauer C, Janlo C, Munoz LE, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014;20:511-7. doi: 10.1038/nm.3547
21. Joosten LA, Netea MG, Fantuzzi G, et al. Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta. Arthritis Rheum. 2009;60(12):3651-62.
22. Chen C-J, Kono H, Golenbock D, et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med. 2007;13:851-6. doi: 10.1038/nm1603
23. Cavalli G, Dinarello CA. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (Oxford). 2015;54:2134-44. doi: 10.1093/rheumatology/kev269
24. Ter Haar NM, Oswald M, Jeyaratnan J, et al. Recommendations for the management of autoinflammatory diseases. Ann Rheum Dis. 2015;74:1636-44. doi: 10.1136/annrheumdis-2015-207546
25. Touitou I, Kone-Paut I. Autoinflammatory diseases. Best Practice and Research. Clin Rheumatol. 2008;22:811-29. doi: 10.1016/j.berh.2008.08.009
26. Stojanovic KS, Delmas Y, Torres PU, et al. Dramatic beneficial effect of interleukin-1 inhibitor treatment in patients with familial Mediterranean fever complicated with amyloidosis and renal failure. Nephrol Dial Transplant. 2012;27:1898-901. doi: 10.1093/ndt/gfr528
27. Moser C, Pohl G, Haslinger I, et al. Successful treatment of familial Mediterranean fever with anakinra and outcome after renal transplantation. Nephrol Dial Transpl. 2009;24:676-8. doi: 10.1093/ndt/gfn646
28. Meinzer U, Quartier P, Alexandra J-F, et al. Interleukin-1 targeting drugs in familial Mediterranean fever: a case series and a review of the literature. Semin Arthritis Rheum. 2011;41:265-71. doi: 10.1016/j.semarthrit.2010.11.003
29. Calligaris L, Marchetti F, Tommasini A, Ventura A. The efficacy of anakinra in an adolescent with colchicine-resistant familial Mediterranean fever. Eur J Pediatr. 2008;167:695-6. doi: 10.1007/s00431-007-0547-3
30. Mitroulis VP, Konstantinidis PT, Ritis K. Anakinra suppresses familial Mediterranean fever crises in a colchicine-resistant patien. Neth J Med. 2008;66:489-91.
31. Estublier KS, Stojanovic J-F, Broussolle BC, Seve P. Myositis in a patient with familial Mediterranean fever and spondyloarthritis successfully treated with anakinra. Joint Bone Spin. 2013;80:645-9. doi: 10.1016/j.jbspin.2013.03.004
32. Akgul O, Kilic E, Kilic G, Ozgocmen S. Efficacy and safety of biologic treatments in familial Mediterranean fever. Amer J Med Sci. 2013;346:137-41. doi: 10.1097/MAJ.0b013e318277083b
33. Hacihamdioglu DO, Ozen S. Canakinumab induces remission in a patient with resistant familial Mediterranean fever. Rheumatology. 2012;51:104. doi: 10.1093/rheumatology/kes021
34. Mitroulis I, Skendros P, Oikonomou A, et al. The efficacy of canakinumab in the treatment of a patient with familial Mediterranean fever and longstanding destructive arthritis. Ann Rheum Dis. 2011;70:1347-8. doi: 10.1136/ard.2010.146878
35. Brizi MG, Galeazzi M, Lucherini OM, et al. Successful treatment of tumor necrosis factor receptor-associated periodic syndrome with canakinumab. Ann Int Med. 2012;156:907-8. doi: 10.7326/0003-4819-156-12-201206190-00027
36. Gattorno M, Obici L, Meini A. Efficacy and safety of canakinumab in patients with TNF receptor-associated periodic syndrome. Arthritis Rheum. 2012;64:749. doi: 10.1136/annrheumdis-2012-eular.2361
37. Lopalco G, Rigant D, Vitale A, et al. Tumor necrosis factor receptor-associated periodic syndrome managed with the couple canakinumab-alendronate. Clin Rheumatol. 2015 Apr;34(4):807-9. doi: 10.1007/s10067-014-2556-8. Epub 2014 Mar 11.
38. Cailliez M, Garaix F, Rousset-Rouviere C, et al. Anakinra is safe and effective in controlling hyperimmunoglobulinaemia D syndrome-associated febrile crisis. J Inherited Metab Dis. 2006;29:763. doi: 10.1007/s10545-006-0408-7
39. Rigante D, Ansuini V, Bertoni B, et al. Treatment with anakinra in the hyperimmunoglobulinemia D periodic fever syndrome. Rheumatol Int. 2006;27:97-100. doi: 10.1007/s00296-006-0164-x
40. Lequerre T, Vittecoq O, Pouplin S, et al. Mevalonate kinase deficiency syndrome with structural damage responsive to anakinra. Rheumatology. 2007;46:1860-2. doi: 10.1093/rheumatology/kem258
41. Galeotti C, Meinzer U, Quartier P, et al. Efficacy of interleukin-1-targeting drugs in mevalonate kinase deficiency. Rheumatology. 2012;51:1855-9. doi: 10.1093/rheumatology/kes097
42. Bodar EJ, Kuijk LM, Drenth JPH, et al. On-demand anakinra treatment is effective in mevalonate kinase deficiency. Ann Rheum Dis. 2011;70:2155-8. doi: 10.1136/ard.2011.149922
43. Bodar EJ, van der Hilst JCH, Drenth JPH, et al. Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model. Neth J Med. 2005;63:260-4.
44. Gomez AR, Couce ML, Garcia-Villoria J, et al. Clinical, genetic, and therapeutic diversity in 2 patients with severe mevalonate kinase deficiency. Pediatrics. 2012;129:e535-9. doi: 10.1542/peds.2010-2192
45. Shendi HM, Walsh D, Edgar JDM. Etanercept and anakinra can prolong febrile episodes in patients with hyperimmunoglobulin D and periodic fever syndrome. Rheumatol Int. 2012;32:249-51. doi: 10.1007/s00296-009-1322-8
46. Teoh SRB, Sharma S, Hogan A, et al. Tailoring biological treatment: anakinra treatment of posterior uveitis associated with the CINCA syndrome. Brit J Ophthalmol. 2007;91:263-4. doi: 10.1136/bjo.2006.0101477
47. Hedrich CM, Bruck N, Paul D, et al. Mutation negative familial cold autoinflammatory syndrome (FCAS) in an 8-year-old boy: clinical course and functional studies. Rheumatol Int. 2012;32:2629-36. doi: 10.1007/s00296-011-2019-3
48. Goldbach-Mansky R, Dailey NJ, Canna SW, et al .Neonatalonset multisystem inflammatory disease responsive to interleukin-1β inhibition. New Eng J Med. 2006;355:581-92. doi: 10.1056/NEJMoa055137
49. Gattorno M, Tassi S, Carta S, et al. Pattern of interleukin-1β secretion in response to lipopolysaccharide and ATP before and after interleukin-1 blockade in patients with CIAS1 mutations. Arthritis Rheum. 2007;56:3138-48. doi: 10.1002/art.22842
50. Neven B, Marvillet I, Terrada C, et al. Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome. Arthritis Rheum. 2010;62:258-67. doi: 10.1002/art.25057
51. Lepore L, Paloni G, Caorsi R, et al. Follow-up and quality of life of patients with cryopyrin-associated periodic syndromes treated with Anakinra. J Pediatrics. 2010;157:310-5. doi: 10.1016/j.jpeds.2010.02.040
52. Miyamae T, Inaba Y, Ishimura G, et al. Effect of anakinra on arthropathy in CINCA/NOMID syndrome. Pediatr Rheumatol Online J. 2010 Mar 16;8:9. doi: 10.1186/1546-0096-8-9
53. Lovell DL, Bowyer SL, Solinger AM. Interleukin-1 blockade by anakinra improves clinical symptoms in patients with neonatalonset multisystem inflammatory disease. Arthritis Rheum. 2005;52:1283-6. doi: 10.1002/art.20953
54. Aubert P, Suarez-Farinas M, Mitsui H, et al. Homeostatic tissue responses in skin biopsies from NOMID patients with constitutive overproduction of IL-1β. PLoS One. 2012;7(11):e49408. doi: 10.1371/journal.pone.0049408. Epub 2012 Nov 30.
55. Balow JE Jr, Ryan JG, Chae JJ, et al. Microarray-based gene expression profiling in patients with cryopyrin-associated periodic syndromes defines a disease-related signature and IL-1-responsive transcripts. Ann Rheum Dis. 2013;72:1064-70. doi: 10.1136/annrheumdis-2012-202082
56. Sibley CH, Plass N, Snow J, et al. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012;64:2375-86. doi: 10.1002/art.34409
57. Hawkins PN, Lachmann HJ, McDermott MF. Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med. 2003;348:2583-4. doi: 10.1056/NEJM200306193482523
58. Rynne M, Maclean C, Bybee A, et al. Hearing improvement in a patient with variant Muckle-Wells syndrome in response to interleukin 1 receptor antagonism. Ann Rheum Dis. 2006;65:533-4. doi: 10.1136/ard.2005.038091
59. Stew BT, Fishpoo SJC, Owens D, Quine S. Muckle-Wells syndrome: a treatable cause of congenital sensorineural hearing loss. B-ENT. 2013;9:161-3.
60. Sabroe RA, Stokes CA, Parker LC, et al. Muckle-Wells syndrome without mutation in exon 3 of the NLRP3 gene, identified by evidence of excessive monocyte production of functional interleukin 1β and rapid response to anakinra. Clin Exp Dermatol. 2013;38:874-7. doi: 10.1111/ced.12186
61. Enriquez R, Sirvent AE, Padilla S, et al. Nephrotic syndrome and AA amyloidosis revealing adult-onset cryopyrin-associated periodic syndrome. Renal Failure. 2013;35:738-41. doi: 10.3109/0886022X.2013.790300
62. Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, et al. Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome. Arthritis Rheum. 2011;63:840-9. doi: 10.1002/art.30149
63. Hawkins PN, Lachmann HJ, Aganna E, McDermott MF. Spectrum of clinical Features in Muckle-Wells syndrome and response to anakinra. Arthritis Rheum. 2004;50:607-12. doi: 10.1002/art.20033
64. Metyas SK, Hoffman HM. Anakinra prevents symptoms of familial cold autoinflammatory syndrome and Raynaud's disease. J Rheumatol. 2006;33:2085-7.
65. Hoffman HM, Rosengren S, Boyle DL, et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet. 2004;364:1779-85. doi: 10.1016/S0140-6736(04)17401-1
66. Kuemmerle-Deschner JB, Wittkowski H, Tyrrell PN, et al. Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens. Arthritis Res Ther. 2013;1:R64. doi: 10.1186/ar4237
67. Kuemmerle-Deschner JB, Lohse P, Koet I, et al. NLRP3 E311K mutation in a large family with Muckle-Wells syndrome-description of a heterogeneous phenotype and response to treatment. Arthritis Res Ther. 2011;13:R196. doi: 10.1186/ar3526
68. Sibley CH, Chioato A, Felix S, et al. A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease. Ann Rheum Dis. 2015;74(9):1714-9. doi: 10.1136/annrheumdis-2013-204877
69. Caorsi R, Lepore L, Zulian F, et al. The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age. Arthritis Res Ther. 2013;15:R33. doi: 10.1186/ar4184
70. Imagawa T, Nishikomori R, Takada H, et al. Safety and efficacy of canakinumab in Japanese patients with phenotypes of cryopyrin-associated periodic syndrome as established in the first openlabel, phase-3 pivotal study (24-week results). Clin Exp Rheum. 2013;31:302-9.
71. Mueller SM, Itin P, Haeuserman P. Muckle-wells syndrome effectively treated with canakinumab: is the recommended dosing schedule mandatory. Dermatology. 2011;223:113-8. doi: 10.1159/000331580
72. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, et al. Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. New Eng J Med. 2009;360:2416-25. doi: 10.1056/NEJMoa0810787
73. Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, et al. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther. 2011;1:R202. doi: 10.1186/ar3535
74. Kuemmerle-Deschner JB, Ramos E, Blank N, et al. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1β mAb) induces sustained remission in pediatric patients with cryopyrinassociated periodic syndrome (CAPS). Arthritis Res Ther. 2011;13: R34. doi: 10.1186/ar3266
75. Kuemmerle-Deschner JB, Hachulla E, Cartwrigh R, et al. Twoyear results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011;70:2095-102. doi: 10.1136/ard.2011.152728
76. Scarpioni R, Rigante D, Cantarini L, et al. Renal involvement in secondary amyloidosis of Muckle-Wells syndrome: marked improvement of renal function and reduction of proteinuria after therapy with human anti-interleukin-1β monoclonal antibody canakinumab. Clin Rheumatol. 2014;34:1311-6. doi: 10.1007/s10067-013-2481-2
77. Pazyar N, Feily A, Yaghoobi R. An overview of interleukin-1 receptor antagonist, anakinra, in the treatment of cutaneous diseases. Curr Clin Pharm. 2012;7:271-5. doi: 10.2174/157488412803305821
78. Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) – a new autoinflammatory syndrome distinct from PAPA syndrome. J Amer Acad Derm. 2012;66:409-15. doi: 10.1016/j.jaad.2010.12.025
79. Brenner M, Ruzicka T, Plewig G, et al. Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra. Bri J Dermatol. 2009;161:1199-201. doi: 10.1111/j.1365-2133.2009.09404.x
80. Dierselhuis MP, Frenkel J, Wulffra NM, Boelens JJ. Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology. 2005;44:406-8. doi: 10.1093/rheumatology/keh479
81. Schellevis MA, Stoffels M, Hoppenreijs EPAH, et al. Variable expression and treatment of PAPA syndrome. Ann Rheum Dis. 2011;70:1168-70. doi: 10.1136/ard.2009.126185
82. Shoham NG, Centola M, Mansfield E, et al. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc Nat Acad Sci USA. 2003;100:13501-6. doi: 10.1073/pnas.2135380100
83. Geusau A, Mothes-Luksch N, Nahavandi H, et al. Identification of a homozygous PSTPIP1 mutation in a patient with a PAPAlike syndrome responding to canakinumab treatment. JAMA Dermatology. 2013;14:209-15. doi: 10.1001/2013.jamadermatol.717
84. Kono H, Chen CJ, Ontiveros F, Rock KL. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J Clin Invest. 2010;120:1939-49. doi: 10.1172/JCI40124
85. Martinon F, Petrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237-41. doi: 10.1038/nature04516
86. Rock KL, Kataoka H, Lai J-J. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol. 2013;9:13-23. doi: 10.1038/nrheum.2012/143
87. Schlesinger N, Alten RE, Bardin T, et al. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, doubleblind trials and their initial extensions. Ann Rheum Dis. 2012;71:1839-48. doi: 10.1136/annrheumdis-2011-200908
88. Wechalekar MD, Vinik O, Moi JUY. The efficacy and safety of treatments for acute gout: results from a series of systematic literature reviews including Cochrane reviews on intraarticular glucocorticoids, colchicine, nonsteroidal antiinflammatory drugs, and interleukin-1 inhibitors. J Rheumatol. 2014;92 (Suppl):15-25. doi: 10.3899/jrheum.140458
89. Eliseev MS, Zhelyabina OV, Mukagova MV, Nasonov E. Canakinumab in patients with chronic tophaceous gout, resistant to current treatment options. Ann Rheum Dis. 2015;74(Suppl 2):541. doi: 10.1136/annrheumdis-2015-eular.3451
90. Елисеев МС, Барскова ВГ, Насонов ЕЛ. Канакинумаб (ингибитор интерлейкина 1β) – прорыв в возможностях противовоспалительной терапии при подагре. Научно-практическая ревматология. 2013;51:428-31 [Eliseev MS, Barskova VG, Nasonov EL. Canakinumab (an interleukin 1β inhibitor) is a breakthrough in the possibilities of anti-inflammatory therapy for gout. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51(4):428-31 (In Russ.)]. doi: 10.14412/1995-4484-2013-1255
91. Bardin T. Canakunumab for the patient with difficult-to-treat gouty arthritis: review of the clinical evidence. Joint Bone Spain. 2015;82:eS9-19. doi: 10.1016/S1297-319X(15)30003-8
92. Keenan RT, O'Brien WR, Lee KH, et al. Prevalence of contraindications and prescription of pharmacologic therapies for gout. Am J Med. 2011;124:155-63. doi: 10.1016/j.amjmed.2010.09.012
93. Neogi T. Gout. N Engl J Med. 2011;64:443-52. doi: 10.1056/NEJMcp1001124
94. Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet. 2011;377:2138-49. doi: 10.1016/S0140-6736(11)60244-4
95. Negrovic PA. Is there a window of opportunity for treatment of systemic juvenile idiopathic arthritis? Arthritis Rheum. 2014;66:1405-13. doi: 10.1002/art.38615
96. Maria ATJ, Le Quellec A, Jorgensen C, et al. Adult onset Still's disease (ASD) in the era of biologic therapies: dichotomous view for cytokine and clinical expressions. Autoimmune Rev. 2014;13:1149-59. doi: 10.1016/j.autrev.2014.08.032
97. Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med.
98. ;201:1479-86. doi: 10.1084/jem.20050473
99. Choi JH, Suh CH, Lee YM, et al Serum cytokine profiles in patients with adult onset Still's disease. J Rheumatol. 2003;30:2422-7.
100. Kotter I, Wacker A, Koch S, et al. Anakinra in patients with treatment-resistant adult-onset Still's disease: four case reports with serial cytokine measurements and a review of the literature. Semin Arthritis Rheum. 2007;37:189-97. doi: 10.1016/j.semarthrit.2007.04.002
101. Никишина ИП, Каледа МИ. Современная фармакотерапия системного ювенильного артрита. Научно-практическая ревматология. 2015;53:84-93 [Nikishina IP, Kaleda MI. Current pharmacotherapy for systemic juvenile arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2015;53:84-93 (In Russ.)]. doi: 10.14412/1995-4484-2015-84-93
102. Tarp S, Amarilyo G, Foeldvari I, et al. Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials. Rheumatology. 2015. doi: 10.1093/rheumatology/kev382. [Epub ahead of print].
103. Kalliolias GD, Liossis SN. The future of the IL-1 receptor antagonist anakinra: from rheumatoid arthritis to adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis. Expert Opin Investig Drugs. 2008;17:349-59. doi: 10.1517/13543784.17.3.349
104. Lequerre T, Quartier P, Rosellini D, et al. Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis. 2008;67:302-8. doi: 10.1136/ard.2007.076034
105. Bruck N, Suttorp M, Kabus M, et al. Rapid and sustained remission of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome through treatment with anakinra and corticosteroids. J Clin Rheumatol. 2011;17:23-7. doi: 10.1097/RHU.0b013e318205092d
106. Laskari K, Tzioufas AG, Moutsopoulos HM. Efficacy and longterm follow-up of IL-1R inhibitor anakinra in adults with Still's disease: a case-series study. Arthritis Res Ther. 2011;13:R91. doi: 10.1186/ar3366
107. Lo Gullo ACA, Pipitone N, Macchioni P, et al. Canakinumab in a case of Adult onset Still's disease: efficacy only on systemic manifestations. Joint Bone Spine. 2014;81:376-7. doi: 10.1016/j.jbspin.2013.12.011
108. Fitzgerald AA, Leclercq SA, Yan A, et al. Rapid responses to anakinra in patients with refractory adult-onset Still's disease. Arthritis Rheum. 2005;52:1794-803. doi: 10.1002/art.21061
109. Giampietro C, Ridene M, Lequerre T, et al. Anakinra in adultonset Still's disease: long-term treatment in patients resistant to conventional therapy. Arthritis Care Res (Hoboken). 2013;65:822-6. doi: 10.1002/acr.21901
110. Kahn P, Cron RQ. Higher-dose anakinra is effective in a case of medically refractory macrophage activation syndrome. J Rheumatol. 2013;40:743-4. doi: 10.3899/jrheum.121098 110. Kalliolias GD, Georgiou PE, Antonopoulos IA, et al. Anakinra treatment in patients with adult-onset Still's disease is fast, effective, safe and steroid sparing: experience from an uncontrolled trial. Ann Rheum Dis. 2007;66:842-3. doi: 10.1136/ard.2006.066381
111. Kontzias A, Efthimiou P. The use of Canakinumab, a novel IL-1beta long-acting inhibitor, in refractory adult-onset Still's disease. Semin Arthritis Rheum. 2012;42:201-5. doi: 10.1016/j.semarthrit.2012.03.004
112. Lahiri M, Teng GG. A case of refractory adult-onset Still's disease treated with anakinra. Int J Rheum Dis. 2010;13:e36-41. doi: 10.1111/j.1756-185X.2010.01474.x
113. Loh NK, Lucas M, Fernandez S, Prentice D. Successful treatment of macrophage activation syndrome complicating adult Still disease with anakinra. Intern Med J. 2012;42:1358-62. doi: 10.1111/imj.12002
114. Naumann L, Feist E, Natusch A, et al. IL1-receptor antagonist anakinra provides long-lasting efficacy in the treatment of refractory adult-onset Still's disease. Ann Rheum Dis. 2010;69:466-7. doi: 10.1136/ard.2009.108068
115. Petryna O, Cush J, Efthimiou P. IL-1 Trap rilonacept in refractory adult onset Still's disease. Ann Rheum Dis. 2012;71:2056-7. doi: 10.1136/annrheumdis-2012-201409
116. Nordstrom D, Knight A, Luukkainen R, et al. Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still's disease. An open, randomized, multicenter study. J Rheumatol. 2012;39:2008-11. doi: 10.3899/jrheum.111549
117. Hong D, Yang Z, Han S, et al. Interleukin 1 inhibition with anakinra in adult-onset Still disease: a meta-analysis of its efficacy and safety. Drug Design Dev Ther. 2014;8:2345-57.
118. De Koning HD, Bodar EJ, van der Meer JW, Simon A. Schnitzler syndrome: beyond the case reports: review and followup of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum. 2007;37:137-48. doi: 10.1016/j.semarthrit.2007.04.001
119. Lipsker D, Veran Y, Grunenberger F, et al. The Schnitzler syndrome. Four new cases and review of the literature. Medicine (Baltimore). 2001;80:37-44. doi: 10.1097/00005792-200101000-00004
120. De Koning HD. Schnitzler's syndrome: lessons from 281 cases. Clin Translat Allerg. 2014;4:41. doi: 10.1186/2045-7022-4-41
121. Simon A, Asli B, Braun-Falco M, et al. Schnitzler's syndrome: diagnosis, treatment, and follow-up. Allergy. 2013;68:562-8. doi: 10.1111/all.12129
122. Pizzirani C, Falzoni S, Govoni M, et al. Dysfunctional inflammasome in Schnitzler's syndrome. Rheumatology (Oxford). 2009;48:1304-8. doi: 10.1093/rheumatology/kep222
123. De Koning HD, Schalkwijk J, Stoffels M. The role of interleukin-1 beta in the pathophysiology of Schnitzler's syndrome. Arthritis Res Ther. 2015;17:187. doi: 10.1186/s13075-015-0696-0
124. Krause K, Weller K, Stefaniak R, et al. Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study. Allergy. 2012;67:943-50. doi: 10.1111/j.1398-9995.2012.02843.x
125. De Koning HD, Schalkwijk J, van der Ven-Jongekrijg J, et al. Sustained efficacy of the monoclonal anti-interleukin-1 beta antibody canakinumab in a 9-month trial in Schnitzler's syndrome. Ann Rheum Dis. 2013;72:1634-8. doi: 10.1136/annrheumdis-2012-202192
126. Besada E, Nossent H. Dramatic response to IL1-RA treatment in longstanding multidrug resistant Schnitzler's syndrome: a case report and literature review. Clin Rheumatol. 2010;29:567-71. doi: 10.1007/s10067-010-1375-9
127. Schuster C, Kranke B, Aberer E, et al. Schnitzler syndrome: response to anakinra in two cases and a review of the literature. Int J Dermatol. 2009;48:1190-4. doi: 10.1111/j.1365-4632.2009.04151.x
128. Ryan JG, de Koning HD, Beck LA, et al. IL-1 blockade in Schnitzler syndrome: ex vivo findings correlate with clinical remission. J Allergy Clin Immunol. 2008;121:260-2. doi: 10.1016/j.jaci.2007.09.021
129. De Koning HD, Bodar EJ, Simon A, et al. Beneficial response to anakinra and thalidomide in Schnitzler's syndrome. Ann Rheum Dis. 2006;65:542-4. doi: 10.1136/ard.2005.045245
130. Martinez-Taboada VM, Fontalba A, Blanco R, Fernandez-Luna JL. Successful treatment of refractory Schnitzler syndrome with anakinra: comment on the article by Hawkins et al. Arthritis Rheum. 2005;52:2226-7. doi: 10.1002/art.21101
131. Pineton de Chambrun M, Wechsler B, Geri G, et al. New insights into the pathogenesis of Behcet's disease. Autoimmun Rev. 2012;11:687-98. doi: 10.1016/j.autrev.2011.11.026
132. Hamzaoui K, Hamza M, Ayed K. Production of TNF-α and IL-1 in active Behcet's disease. J Rheumatol. 1990;17:1428-9.
133. Pay S, Erdem H, Pekel A, et al. Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behcet's disease. Does interleukin-1β play a major role in Behcet's synovitis? Rheumatol Int. 2006;26:608-13. doi: 10.1007/s00296-005-0040-0
134. Castrichini M, Lazzerini PE, Gamberucci A, et al. The purinergic P2×7 receptor is expressed on monocytes in Behcet's disease and is modulated by TNF-α. Eur J Immunol. 2014;44:227-38. doi: 10.1002/eji.201343353
135. Cantarini L, Vitale A, Scalini P, et al. Anakinra treatment in drug-resistant Behcet's disease: a case series. Clin Rheumatol. 2015 Jul;34(7):1293-301. doi: 10.1007/s10067-013-2443-8. Epub 2013 Dec 5.
136. Caso F, Rigante D, Vitale A, et al. Efficacy of anakinra in refractory Behcet's disease sacroiliitis. Clin Expl Rheumatol. 2014;324 (Suppl 84):S171.
137. Bilginer Y, Ayaz NA, Ozen S. Anti-IL-1 treatment for secondary amyloidosis in an adolescent with FMF and Behcet's disease. Clin Rheumatol. 2010;29:209-10. doi: 10.1007/s10067-009-1279-8
138. Botsios C, Sfriso P, Furlan A, et al. Resistant Behcet disease responsive to anakinra. Ann Int Med. 2008;149:284-6. doi: 10.7326/0003-4819-149-4-200808190-00018
139. Emmi G, Silvestri E, Cameli AM, et al. Anakinra for resistant Behcet uveitis: why not? Clin Exp Rheumatol. 2013;31(Suppl 77):S152-3.
140. Cantarini L, Lopalco G, Caso F, et al. Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behcet's disease. Autoimm Rev. 2015;14:1-9. doi: 10.1016/j.autrev.2014.08.008
141. Vitale A, Rigante D, Caso F, et al. Inhibition of interleukin-1 by canakinumab as a successful mono-drug strategy for the treatment of refractory Behcet's disease: a case series. Dermatology. 2014;228:211-4. doi: 10.1159/000358125
142. Cantarini L, Vitale A, Borri M, et al. Successful use of canakinumab in a patient with resistant Behcet's disease. Clin Exp Rheumatol. 2012;30(Suppl 72):S115.
143. Gü l A, Tugal-Tutkun I, Dinarello CA, et al. Interleukin-1β-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet's disease: an open-label pilot study. Ann Rheum Dis. 2012;71:563-6. doi: 10.1136/annrheumdis-2011-155143
144. Mansouri B, Richards L, Menter A. Treatment of two patients with generalized pustular psoriasis with the interleukin-1β inhibitor gevokizumab. Br J Dermatol. 2015;173:239-41. doi: 10.1111/bjd.13614
145. Wendling D, Prati C, Aubin F. Anakinra treatment of SAPHO syndrome: short-term results of an open study. Ann Rheum Dis. 2012;71:1098-100. doi: 10.1136/annrheumdis-2011-200743
146. Rech J, Manger B, Lang B, et al. Adult-onset Still's disease and chronic recurrent multifocal osteomyelitis: a hitherto undescribed manifestation of autoinflammation. Rheumatol Int. 2012;32:1827-9. doi: 10.1007/s00296-011-2020-x
147. Wu Y, Li H, Jiang Z, Lai Y. The interleukin-1 family: a key regulator in the pathogenesis of psoriasis. Austin J Clin Immunol. 2014;5:id1023.
148. Ariza M-E, Williams MV, Wong HK. Targeting IL-17 in psoriasis: from cutaneous immunobiology to clinical application. Clin Immunol. 2013;146:131-9. doi: 10.1016/j.clim.2012.12.004
149. Anderson KS, Petersson S, Wong J, et al. Elevation of serum epidermal growth factor and interleukin 1 receptor antagonist in active psoriasis vulgaris. Br J Dermatol. 2010;163:1085-9. doi: 10.1111/j.1365-2133.2010.09990.x
150. Balato A, Schiattarella M, Lembo S, et al. Interleukin-1 family members are enhanced in psoriasis and suppressed by vitamin D and retinoic acid. Arch Dermatol Res. 2013;305:255-62. doi: 10.1007/s00403-013-1327-8
151. Johnston A, Xing X, Guzman AM, et al. IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression. J Immunol. 2011;186:2613-22. doi: 10.4049/jimmunol.1003162
152. Tamilselvi E, Haripriya D, Hemamalini M, et al. Association of disease severity with IL-1 levels in methotrexate-treated psoriasis patients. Scand J Immunol. 2013;78:545-53. doi: 10.1111/sji.12117
153. Dungan LS, Mills KH. Caspase-1-processed IL-1 family cytokines play a vital role in driving innate IL-17. Cytokine. 2011;56:126-32. doi: 10.1016/j.cyto.2011.07.007
154. Sutton CE, Lalor SJ, Sweeney CM, et al. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity. 2009;31:331-41. doi: 10.1016/j.immuni.2009.08.001
155. Groves RW, Mizutani H, Kieffer JD, Kupper TS. Inflammatory skin disease in transgenic mice that express high levels of interleukin 1 alpha in basal epidermis. Proc Natl Acad Sci USA. 1995;92:11874-8. doi: 10.1073/pnas.92.25.11874
156. Groves RW, Rauschmayr T, Nakamura K, et al. Inflammatory and hyperproliferative skin disease in mice that express elevated levels of the IL-1 receptor (type I) on epidermal keratinocytes. Evidence that IL-1-inducible secondary cytokines produced by keratinocytes in vivo can cause skin disease. J Clin Invest. 1996;98:336-44. doi: 10.1172/JCI118797
157. Shepherd J, Little MC, Nicklin MJ. Psoriasis-like cutaneous inflammation in mice lacking interleukin-1 receptor antagonist. J Invest Dermatol. 2004;122:665-9. doi: 10.1111/j.0022-202X.2004.22305.x
158. Mee JB, Johnson CM, Morar N, et al. The psoriatic transcriptome closely resembles that induced by interleukin-1 in cultured keratinocytes: dominance of innate immune responses in psoriasis. Am J Pathol. 2007;171:32-42. doi: 10.2353/ajpath.2007.061067
159. Pontifex EK, Gerlag DM, Gogarty M, et al. Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy: a single centre, open-label study. Arthritis Res Ther. 2011;13:R7. doi: 10.1186/ar3228
160. Jung N, Hellmann M, Hoheisel R, et al. An open-label pilot study of the efficacy and safety of anakinra in patients with psoriatic arthritis refractory to or intolerant of methotrexate (MTX). Clin Rheumatol. 2011;29:1169-73. doi: 10.1007/s10067-010-1504-5
161. Bresnihan B, Alvaro-Gracia JM, Cobby M, et al. Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum. 1998;41:2196-204. doi: 10.1002/1529-0131(199812)41:12<2196::AIDART15>3.0.CO;2-2
162. Cohen S, Moreland BW, Cush JJ, et al. A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate. Ann Rheum Dis. 2004;63:1062-8. doi: 10.1136/ard.2003.016014
163. Cohen S, Hurd E, Cush J, et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebocontrolled trial. Arthritis Rheum. 2002;46:614-24. doi: 10.1002/art.10141
164. Mertens M, Singh JA. Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol. 2009;36:1118-25. doi: 10.3899/jrheum.090074
165. Fleischmann RM, Schechtman J, Bennett R, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist (rmetHuIL-1ra), in patients with rheumatoid arthritis: a large, international, multicenter, placebo-controlled trial. Arthritis Rheum. 2003;48:927-34. doi: 10.1002/art.10870
166. Abramson SB, Amin A. Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology. 2001;41:972-80. doi: 10.1093/rheumatology/41.9.972
167. Cunnane G, Madigan A, Murphy E, et al. The effects of treatment with interleukin-1 receptor antagonist on the inflamed synovial membrane in rheumatoid arthritis. Rheumatology. 2001;40:62-9. doi: 10.1093/rheumatology/40.1.62
168. Bresnihan B, Newmark R, Robbins S, Genant HK. Effects of anakinra monotherapy on joint damage in patients with rheumatoid arthritis. Extension of a 24-week randomized, placebo-controlled trial. J Rheumatol. 2004;31:1103-11.
169. Jiang Y, Genant HK, Watt I, et al. A multicenter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis: radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum. 2000;43:1001-9. doi: 10.1002/1529-0131(200005)43:5<1001::AIDANR7>3.0.CO;2-P
170. Horai R, Saijo S, Tanioka H, et al. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J Exp Med. 2000;191:313-20. doi: 10.1084/jem.191.2.313
171. Wood DD, Ihrie EJ, Dinarello CA, Cohen PL. Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum. 1983;26:975-83. doi: 10.1002/art.1780260806
172. Koch AE, Kunkel SL, Chensue SW, et al. Expression of interleukin-1 and interleukin-1 receptor antagonist by human rheumatoid synovial tissue macrophages. Clin Immunol Immunopathol. 1992;65:23-9. doi: 10.1016/0090-1229(92)90243-H
173. Firestein GS, Berger AE, Tracey DE, et al. IL-1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium. J Immunol. 1992;149:1054-62.
174. Joosten LA, Helsen MM, van de Loo FA, van den Berg WB. Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice: a comparative study using anti-TNFα, anti-IL-1α/β, and IL-1Ra. Arthritis Rheum. 1996;39:797-809. doi: 10.1002/art.1780390513
175. Zwerina J, Hayer S, Tohidast-Akrad M, et al. Single and combined inhibition of tumor necrosis factor, interleukin-1, and RANKL pathways in tumor necrosis factor-induced arthritis: effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis Rheum. 2004;50:277-90. doi: 10.1002/art.11487
176. Choulaki C, Papadaki G, Repa A, et al. Enhanced activity of NLRP3 inflammasome in peripheral blood cells of patients with active rheumatoid arthritis. Arthritis Res Ther. 2015;17:257. doi: 10.1186/s13075-0775-2
177. Nam JL, Ramino S, Gaujoux-Viala C, et al. Extended report: Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2014;73:516-28. doi: 10.1136/annrheumdis-2013-204577
178. Singh JA, Christensen R, Wells GA, et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews (Protocol). Cochrane Database of Systematic Reviews. 2009;2:CD007848. doi: 10.1002/14651858.CD007848
179. Alten R, Gomez-Reino J, Durez P, et al. Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, phase II, dose-finding study. BMC Musculoskelet Disord. 2011;12:153. doi: 10.1186/1471-2474-12-153
180. Demin I, Hamren B, Luttringer O, et al. Longitudinal modelbased meta-analysis in rheumatoid arthritis: an application toward model-based drug development. Clin Pharm Ther. 2012;92:352-9. doi: 10.1038/clpt.2012.69
181. Orlowsky EW, Kraus VB. The role of innate immunity in osteoarthritis: when our first line of defense goes on the offensive. J Rheumatol. 2015;42:363-71. doi: 10.3899/jrheum.140382
182. Wang X, Hunter D, Xu J, Ding C. Metabolic triggered inflammation in osteoarthritis RSS Download PDF Get rights and content. Osteoarthr Cartilage. 2015;23:22-30. doi: 10.1016/j.joca.2014.10.002
183. Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol. 2015;11:35-44. doi: 10.1038/nrrheum.2014.162
184. Kusano K, Miyaura C, Inada M, et al. Regulation of matrix metalloproteinases (MMP-2, -3, -9, and -13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption. Endocrinology. 1998;139:1338-45. doi: 10.1210/endo.139.3.5818
185. Goldring MB, Birkhead JR, Suenet LF, et al. Interleukin-1 beta-modulated gene expression in immortalized human chondrocytes. J Clin Invest. 1994;94:2307-16. doi: 10.1172/JCI117595
186. Tyler JA. Articular cartilage cultured with catabolin (pig interleukin 1) synthesizes a decreased number of normal proteoglycan molecules. Biochem J. 1985;227:869-78. doi: 10.1042/bj2270869
187. Attur MG, Patel IR, Patel RN, et al. Autocrine production of IL-1β by human osteoarthritis-affected cartilage and differential regulation of endogenous nitric oxide, IL-6, prostaglandin E2, and IL-8. Proc Assoc Am Physicians. 1998;110:65-72.
188. Pelletier JP, Caron JP, Evans C, et al. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum. 1997;40:1012-9. doi: 10.1002/art.1780400604
189. Fernandes J, Tardif G, Martel-Pelletier J, et al. In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: prevention of osteoarthritis progression. Am J Pathol. 1999;154:1159-69. doi: 10.1016/S0002-9440(10)65368-0
190. Attur M, Wang H-Y, Kraus VB, et al. Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations. Ann Rheum Dis. 2010;69:856-61. doi: 10.1136/ard.2009.113043
191. Kerkhof HJ, Doherty M, Arden NK, et al. Large-scale metaanalysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis. Osteoarthr Cartil. 2011;19:265-71. doi: 10.1016/j.joca.2010.12.003
192. Chevalier X, Goupille P, Beaulieu AD, et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2009;61:344-52. doi: 10.1002/art.24096
193. Cohen SB, Proudman S, Kivitz AJ, et al. A randomized, doubleblind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of knee. Arthritis Res Ther. 2011;13:R125. doi: 10.1186/ar3430 194. Heiland GR, Aigner E, Dallos T, et al. Synovial immunopathology in haemochromatosis arthropathy. Ann Rheum Dis. 2010;69:1214-9. doi: 10.1136/ard.2009.120204
194. Latourte A, Frazier A, Briere C, et al. Interleukin-1 receptor antagonist in refractory haemochromatosis-related arthritis of the hands. Ann Rheum Dis. 2013;72:783-4. doi: 10.1136/annrheumdis-2012-202738
195. Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med. 1999; 340: 115. doi: 10.1056/NEJM199901143400207
196. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685-95. doi: 10.1056/NEJMra043430
197. Libby P, Ridker PM, Hansson GK. Progresss and challenges in translating the biology of atherosclerosis. Nature. 2011;473:317-25. doi: 10.1038/nature10146
198. Skeoch S, Bruce IA. Atherosclerosis in rheumatoid arthritis: is it all about inflammation? Nat Rev Rheumatol. 2015 Jul;11(7):390-400. doi: 10.1038/nrrheum.2015.40. Epub 2015 Mar 31.
199. Nurmohamed NT, Heslinga M, Kitas GD. Cardiovascular comorbidity in rheumatic diseases. Nat Rev Rheumatol. 2015;11:693-704. doi: 10.1038/nrrheum.2015.112
200. Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464:1357-61. doi: 10.1038/nature08938
201. Rajamaki K, Lappalainen J, Oorni K, et al. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS One. 2010;5:e11765. doi: 10.1371/journal.pone.0011765
202. Xiao H, Lu M, Lin TY, et al. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility. Circulation. 2013;128:632-42. doi: 10.1161/CIRCULATIONAHA.113.002714
203. Van Tassel BW, Toldo S, Mezzaroma E, Abbate A. Targeting interleukin-1 in heart disease. Circulation. 2013;128:1910-3. doi: 10.1161/CIRCULATION.113.003199
204. Roubille F, Busseuil D, Shi Y. The interleukin-1β modulator gevokizumab reduces neointimal proliferation and improves reendothelialization in a rat carotid denudation model. Atherosclerosis. 2014;236:277-85. doi: 10.1016/j.atherosclerosis.2014.07.012
205. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory
206. Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597-605. doi: 10.1016/j.ahj.2011.06.012
207. Ridker PM, Howard CP, Walter V, et al. Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012;126:2739-48. doi: 10.1161/CIRCULATIONAHA.112.122556
208. The Interleukin 1 genetics Consortium. Cardiometabolic effects of genetic upregulation of the interleukin 1receptor antagonists: a Mendelian randomization analysis. Lancet Diabetes Endocrinol. 2015;3:243-53. doi: 10.1016/S2213-8587(15)00034-0
209. Rader DJ. IL-1 and atherosclerosis: a murine twist to an evolving human story. J Clin Invest. 2012;122:27-30. doi: 10.1172/JCI61163
210. Frangogiannis N. Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts. Discoveries J. 2015;3:e41. doi: 10.15190/d.2015.33
211. Lugrin J, Parapanov R, Rosenblatt-Velin N, et al. Cutting edge: IL-1alpha is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction. J Immunol. 2015;194:499-503. doi: 10.4049/jimmunol.1401948
212. Abbate A, Kontos MC, Grizzard JD, et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol. 2010;105:1371-7. doi: 10.1016/j.amjcard.2009.12.059
213. Abbate A, van Tassell BW, Biondi-Zoccai G, et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study. Am J Cardiol. 2013;111:1394-400. doi: 10.1016/j.amjcard.2013.01.287
214. Abbate A, Kontos MC, Abouzaki NA, et al. Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies). Am J Cardiol. 2015;115:288-92. doi: 10.1016/j.amjcard.2014.11.003
215. Morton AC, Rothman AM, Greenwood JP, et al. The effect of Interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study. Eur Heart J. 2015;36:377-4. doi: 10.1093/eurheartj/ehu272
216. Van Tassell BW, Arena R, Biondi-Zoccai G, et al. Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study). Am J Cardiol. 2014;113:321-27. doi: 10.1016/j.amjcard.2013.08.047
217. Herder C, Dalmas E, Boni-Schnetzler M, Donath MY. The IL-1 pathway in type 2 diabetes and cardiovascular complications Trends Endocrinol Metab. 2015;26:551-63. doi: 10.1016/j.tem.2015.08.001
218. Masters, SL, Dunne A, Subramanian SL, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat Immunol. 2010;11:897-904. doi: 10.1038/ni.1935
219. Herder C, Carstensen M, Ouwens DM, et al. Anti-inflammatory cytokines and risk of type 2 diabetes. Diabetes Obes Metab. 2013;15:39-50. doi: 10.1111/dom.12155
220. Carstensen M, Herder C, Kivimä ki M, et al. Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes. 2010;59:1222-7. doi: 10.2337/db09-1199
221. Patti G, Di Sciascio G, D'Ambrosio A, et al. Prognostic value of interleukin-1 receptor antagonist in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2002;89:372-6. doi: 10.1016/S0002-9149(01)02254-8
222. Blankenberg S, Zeller T, Saarela O, et al; MORGAM Project. Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project. Circulation. 2010;121:2388-97. doi: 10.1161/CIRCULATIONAHA.109.901413
223. Ligthart S, Sedaghat S, Ikram MA, et al. EN-RAGE: a novel inflammatory marker for incident coronary heart disease. Arterioscler Thromb Vasc Biol. 2014;34:2695-9. doi: 10.1161/ATVBAHA.114.304306
224. Looker HC, Colombo M, Agakov F, et al; SUMMIT Investigators. Protein biomarkers for the prediction of cardiovascular disease in type 2 diabetes. Diabetologia. 2015;58:1363-71. doi: 10.1007/s00125-015-3535-6
225. Hensen J, Howard CP, Walter V, Thuren T. Impact of interleukin-1β antibody (canakinumab) on glycaemic indicators in patients with type 2 diabetes mellitus: results of secondary endpoints from a randomized, placebo-controlled trial. Diabetes Metab. 2013;39:524-31. doi: 10.1016/j.diabet.2013.07.003
226. Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356:1517-26. doi: 10.1056/NEJMoa065213
227. Larsen CM, Faulenbach M, Vaag A, et al. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care. 2009;32:1663-8. doi: 10.2337/dc09-0533
228. Van Asseldonk EJ, Stienstra R, Koenen TB, et al. Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2011;96:2119-26. doi: 10.1210/jc.2010-2992
229. Van Asseldonk EJ, van Poppel PC, Ballak DB, et al. One week treatment with the IL-1 receptor antagonist anakinra leads to a sustained improvement in insulin sensitivity in insulin resistant patients with type 1 diabetes mellitus. Clin Immunol. 2015;160:155-62. doi: 10.1016/j.clim.2015.06.003
230. Sloan-Lancaster J, Abu-Raddad E, Polzer J, et al. Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1β antibody, in patients with type 2 diabetes. Diabetes Care. 2013;36:2239-46. doi: 10.2337/dc12-1835
231. Cavelti-Weder C, Babians-Brunner A, Keller C, et al. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care. 2012;35:1654-62. doi: 10.2337/dc11-2219
232. Rissanen A, Howard CP, Botha J, Thuren T; Global Investigators. Effect of anti-IL-1β antibody (canakinumab) on insulin secretion rates in impaired glucose tolerance or type 2 diabetes: results of a randomized, placebo-controlled trial. Diabetes Obes Metab. 2012;14:1088-96. doi: 10.1111/j.1463-1326.2012.01637.x
233. Stahel M, Becker M, Graf N, Michels S. Systemic interleukin 1β inhibition in proliferative diabetic retinopathy: A Prospective Open-Label Study Using Canakinumab. Retina. 2016 Feb;36(2):385-91. doi: 10.1097/IAE.0000000000000701
234. Timper K, Seelig E, Tsakiris DA, Donath MY. Safety, pharmacokinetics, and preliminary efficacy of a specific anti-IL-1alpha therapeutic antibody (MABp1) in patients with type 2 diabetes mellitus. J Diabetes Complications. 2015 Sep-Oct;29(7):955-60. doi: 10.1016/j.jdiacomp.2015.05.019. Epub 2015 Jun 3.
235. Herder C, Bongaerts BW, Rathmann W, et al. Association of subclinical inflammation with polyneuropathy in the older population: KORA F4 study. Diabetes Care. 2013;36:3663-70. doi: 10.2337/dc13-0382
236. Agrawal NK, Kant S. Targeting inflammation in diabetes: newer therapeutic options. World J Diabetes. 2014 Oct 15;5(5):697-710. doi: 10.4239/wjd.v5.i5.697
237. Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet. 2011;378:1015-26. doi: 10.1016/S0140-6736(11)60988-4
238. Rovina N, Koutsoukou A, Koulouris NG. Inflammation and immune response in COPD: where do we stand? Mediators Inflamm. 2013;2013:413735. doi: 10.1155/2013/413735. Epub 2013 Jul 15
239. Birrell MA, Eltom S. The role of the NLRP3 inflammasome in the pathogenesis of airway disease. Pharmacol Ther. 2011;130:364-70. doi: 10.1016/j.pharmthera.2011.03.007
240. Rogliani P, Calzetta L, Ora J, Metara MG. Canakinumab for the treatment of chronic obstructive pupmonary disease. Pulm Pharmacol Ther. 2015;31:15-27. doi: 10.1016/j.pupt.2015.01.005
241. Church LD, McDermott MF. Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther. 2009;11:81-9.
242. Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation. 1999;100:2124-6. doi: 10.1161/01.CIR.100.21.2124
243. Ikonomidis I, Tzortzis S, Lekakis J, et al. Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis. Heart. 2009;95:1502-7. doi: 10.1136/hrt.2009.168971
244. Ikonomidis I, Lekakis JP, Nikolaou M, et al. Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis. Circulation. 2008;117:2662-9. doi: 10.1161/CIRCULATIONAHA.107.731877
245. Ikonomidis I, Tzortzis S, Andreadou I, et al. Increased benefit of interleukin-1 inhibition on vascular function, myocardial deformation, and twisting in patients with coronary artery disease and coexisting rheumatoid arthritis. Circ Cardiovasc Imaging. 2014;7:619-28. doi: 10.1161/CIRCIMAGING.113.001193
246. Abbate A, Canada JM, van Tassel BW, et al. Interleukin-1 blockade in rheumatoid arthritis and heart failure: A missed opportunity? Int J Cardiol. 2014;171:e125-6. doi: 10.1016/j.ijcard.2013.12.07
247. Arena R, Myers J, Guazzi M. The clinical and research applications of aerobic capacity and ventilatory efficiency in heart failure: an evidence-based review. Heart Fail Rev. 2008;13:245-69. doi: 10.1007/s10741-007-9067-5
248. Swank AM, Horton J, Fleg JL, et al. Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training. Circ Heart Fail. 2012;5:579-85. doi: 10.1161/CIRCHEARTFAILURE.111.965186
249. Mann DL. Targeted anticytokine therapy and the failing heart. Am J Cardiol. 2005;95:9C-16C. doi: 10.1016/j.amjcard.2005.03.007
250. Кондратьева ЛВ, Попкова ТВ, Насонов ЕЛ. Метаболический синдром при ревматоидном артрите. Научно-практическая ревматология. 2013;51:302-12 [Kondratyeva LV, Popkova TV, Nasonov EL. Metabolic syndrome in rheumatoid arthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2013;51:302-12 (In Russ.)]. doi: 10.14412/1995-4484-2013-1506
251. Ruscitti P, Cipriani P, Di Benedetto P. Monocytes from patients with rheumatoid arthritis and type 2 diabetes mellitus display an increased production of interleukin (IL)-1β via the nucleotidebinding domain and leucine-rich repeat containing family pyrin 3(NLRP3)-inflammasome activation: a possible implication for therapeutic decision in these patients. Clin Exp Immunol 2015;182:35-44. doi: 10.1111/cei.12667
252. Ruscitti P, Cipriani P, Cantarini L, et al. Efficacy of inhibition of IL-1 in patients with rheumatoid arthritis and type 2 diabetes mellitus: a two case report and review of literature. J Med Case Rep. 2015 Jun 2;9:123. doi: 10.1186/s13256-015-0603-y
253. Crisan TO, Cleophas MCP, Oosting M, et al. Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra. Ann Rheum Dis. 2015 Feb 3. doi: 10.1136/annrheumdis-2014-206564. [Epub ahead of print].
254. Stern SM, Ferguson PJ. Autoinflammatory bone diseases. Rheum Dis Clin North Am. 2013;39:735-49. doi: 10.1016/j.rdc.2013.05.002
255. Xiao J, Fu C, Zhang X, et al. Soluble monosodium urate, but not its crystal, induces toll like receptor 4-dependent immune activation in renal mesangial cells. Mol Immunol. 2015;66:310-8. doi: 10.1016/j.molimm.2015.03.250
256. Panoulas VF, Douglas KM, Milionis HJ, et al. Serum uric acid is independently associated with hypertension in patients with rheumatoid arthritis. J Hum Hypertens. 2008;22:177-82. doi: 10.1038/sj.jhh.1002298
257. Daoussis D, Panoulas V, Toms T, et al. Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis. Arthritis Res Ther. 2009;11:R116. doi: 10.1186/ar2775
258. Panoulas V, Milionis HJ, Douglas KM, et al. Association of serum uric acid with cardiovascular disease in rheumatoid arthritis. Rheumatology (Oxford). 2007;46:1466-70. doi: 10.1093/rheumatology/kem159
259. Daoussis D, Kitas GD. Uric acid and cardiovascular risk in rheumatoid arthritis. Rheumatology (Oxford). 2011;50:1354-5. doi: 10.1093/rheumatology/keq388
260. Petsch C, Araujio E, Englbrecht M, et al. Prevalence of monosodium urate deposits in a population of rheumatoid arthritis patients with hyperuricemia. Semin Arthritis Rheum. 2015 Dec 2. doi: 10.1016/j.semarthrit.2015.11.014. [Epub ahead of print].
261. Denoble AE, Huffman KM, Stabler TV, et al. Uric acid a danger signal of increasing risk for osteoarthritis through inflammasome activation. Proc Nat Acad Sci USA. 2011;108:2088-93. doi: 10.1073/pnas.1012743108
262. Cicero AF, Salvi P, D'Addato S, et al. Brisighella Heart Study. Association between serum uric acid, hypertension, vascular stiffness and subclinical atherosclerosis: data from the Brisighella Heart Study. J Hypertens. 2014;32:57-64. doi: 10.1097/HJH.0b013e328365b916
263. Athyros VG, Mikhailidis DP. Uric acid, chronic kidney disease and type 2 diabetes: A cluster of vascular risk factors. J Diabet Compl. 2014;28:122-3. doi: 10.1016/j.jdiacomp.2013.11.012
264. Gustafsson D, Unwin R. The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality. BMC Nephrol. 2013;14:164. doi: 10.1186/1471-2369-14-164
265. Chaudhary K, Malhotra K, Sowers J, et al. Uric acid – key ingredient in the recipe for cardiorenal metabolic syndrome. Cardiorenal Med. 2013;3:208-20. doi: 10.1159/000355405
266. De Bosch BJ, Kluth O, Fujiwara H, et al. Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9. Nat Commun. 2014;5:4642. doi: 10.1038/ncomms5642
267. Breshihan B. The safety and efficacy of interleukin-1 receptor antagonist in the treatment of rheumatoid arthritis. Semin Arthritis Rheum. 2001 Apr;30(5 Suppl 2):17-20. doi: 10.1053/sarh.2001.23701
268. Souto A, Maneiro JR, Gomez-Reino JJ. Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases. Rheumatology (Oxford). 2016 Mar;55(3):523-34. doi: 10.1093/rheumatology/kev374. Epub 2015 Oct 21.
269. Dinarello CA, Simon A, Meer van der JWS. Treating inflammation by blocking interleukin-1 in a broad spectrum of disease. Nat Rev Drug Discov. 2012;11:633-52. doi: 10.1038/nrd3800
270. Blech M, Peter D, Fischer P, et al. One target-two different binding model: structural insight into gevolkizumab and canakinumab interactions to interleukin-1β. J Mol Biol. 2013;425:94-111. doi: 10.1016/j.jmb.2012.09.021
271. Coleman KM, Gudjonsson JE, Stecher M. Open-label trial of MABp1, a true human monoclonal antibody targeting interleukin 1β, for the treatment of psoriasis. JAMA Dermatol. 2015;151:555-6. doi: 10.1001/jamadermatol.2014.5391
272. Shao B-Z, Xu Z-Q, Han B-Z, et al. NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol. 2015;6: article 262. doi: 10.3389/fpharm.2015.00262
273. Frenzel E, Wrenger S, Immenschuh S, et al. Acute-phase protein α1-antitrypsin – a novel regulator of angiopoietin-like protein 4 transcription and secretion. J Immunol. 2014;192:5354-62. doi: 10.4049/jimmunol.1400378
274. Joosten LA, Crisan TO, Azam T, et al. α-1-anti-trypsin-Fc fusion protein ameliorates gouty arthritis by reducing release and extracellular processing of IL-1β and by the induction of endogenous IL-1Ra. Ann Rheum Dis. 2015 Jul 14. doi: 10.1136/annrheumdis-2014-206966. [Epub ahead of print].
275. Edwards NL, So A. Emerging therapies for gout. Rheum Dis Clin N Amer. 2014;40:375-87. doi: 10.1016/j.rdc.2014.01.013
276. Giamarellos-Bourboulis EJ, Mouktarond M, Bodar E, et al. Crystals of monosodium urate monohydrate enhance lipopolysaccharide-induced release of interleukin 1β by mononuclear cells through a caspase 1-mediated process. Ann Rheum Dis. 2009;68:273-8. doi: 10.1136/ard.2007.082222
Рецензия
Для цитирования:
Насонов Е.Л., Елисеев М.С. Роль интерлейкина 1 в развитии заболеваний человека. Научно-практическая ревматология. 2016;54(1):60-77. https://doi.org/10.14412/1995-4484-2016-60-77
For citation:
Nasonov E.L., Eliseev M.S. ROLE OF INTERLEUKIN 1 IN THE DEVELOPMENT OF HUMAN DISEASES. Rheumatology Science and Practice. 2016;54(1):60-77. (In Russ.) https://doi.org/10.14412/1995-4484-2016-60-77
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