Интерлейкин 6 как патогенетический фактор, опосредующий формирование клинических проявлений, и мишень для терапии ревматических заболеваний и депрессивных расстройств
https://doi.org/10.14412/1995-4484-2019-318-327
Аннотация
В обзоре обобщены современные представления о ключевой роли интерлейкина 6 (ИЛ6) в патогенезе ревматических заболеваний (РЗ) и депрессивных расстройств. Подробно рассмотрены механизмы участия ИЛ6 в формировании клинико-лабораторных проявлений РЗ и депрессии; влияние провоцирующих и предрасполагающих стрессовых факторов, включая психические травмы в детском возрасте, повышающих риск раз- вития РЗ и депрессии, на выработку ИЛ6. Особое внимание уделено рассмотрению перспектив использования ингибиторов ИЛ6 в терапии депрессии.
Об авторах
Т. А. ЛисицынаРоссия
115522, Москва, Каширское шоссе, 34А.
Д. Ю. Вельтищев
Россия
107076, Москва, ул. Потешная, 3, к. 10.
117997, Москва, ул. Островитянова, 1.
А. М. Лила
Россия
115522, Москва, Каширское шоссе, 34А.
Е. Л. Насонов
Россия
115522, Москва, Каширское шоссе, 34А.
119991, Москва, ул. Трубецкая, 8, стр. 2.
Список литературы
1. Choy EHS, Calabrese LH. Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid arthritis. Rheumatology. 2018;57:1885-95. doi: 10.1093/rheumatology/kex391
2. Dougados M, Soubrier M, Antunez A, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis. 2014;73(1):62-8. doi: 10.1136/annrheumdis-2013-204223
3. Matcham F, Rayner L, Steer S, Hotopf M. The prevalence of depression in rheumatoid arthritis: a systematic review and metaanalysis. Rheumatology (Oxford). 2014;53(3):578-9. doi: 10.1093/rheumatology/ket439
4. Marrie RA, Hitchon CA, Walld R. Increased Burden of Psychiatric Disorders in Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2018 Jul;70(7): 970-8. doi: 10.1002/acr.23539
5. Matcham F, Davies R, Hotopf M, et al. The relationship between depression and biologic treatment response in rheumatoid arthritis: An analysis of the British Society for Rheumatology Biologics Register. Rheumatology. 2018;57:835-43. doi: 10.1093/rheumatology/kex528
6. Насонов ЕЛ, Александрова ЕН, Авдеева АС, Панасюк ЕЮ. Ингибиция интерлейкина 6 – новые возможности фармакотерапии иммуновоспалительных ревматических заболеваний. Научно-практическая ревматология. 2013;51(4): 416-27 [Nasonov EL, Aleksandrova EN, Avdeeva AS, Panasyuk EYu. Interleukin 6 inhibition: new possibilities of pharmacotherapy for immunoinflammatory rheumatic diseases. Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(4):416-27 (In Russ.)]. doi: 10.14412/1995-4484-2013-1254
7. Насонов ЕЛ, Мазуров ВИ, Усачева ЮВ и др. Разработки отечественных оригинальных генно-инженерных биологических препаратов для лечения иммуновоспалительных ревматических заболеваний. Научно-практическая ревматология. 2017;55(2):201-10 [Nasonov EL, Mazurov VI, Usacheva YuV, et al. Developments of Russian original biological agents for the treatment of immunoinflammatory rheumatic diseases. Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2017;55(2):201-10 (In Russ.)]. doi: 10.14412/1995-4484-2017-201-210
8. Maes M. Major depression and activation of the inflammatory response system. Adv Exp Med Biol. 1999;461:25-46.
9. Hodes GE, Menard C, Russo SJ. Integrating Interleikin-6 into depression diagnosis and treatment. Neurobiol Stress. 2016;4:15- 22. doi: 10.1016/j.ynstr.2016.03.003
10. Gananc L, Oquendo MA, Tyrka AR, et al. The role of cytokines in the pathophysiology of suicidal behavior. Psychoneuroendocrinology. 2016;63:296-310. doi: 10.1016/j.psyneuen.2015.10.008
11. Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67:446-57. doi: 10.1016/j.biopsych.2009.09.033
12. Haapakoski R, Mathieu J, Ebmeier KP, et al. Cumulative metaanalysis of interleukins 6 and 1beta, tumour necrosis factor alpha and C reactive protein in patients with major depressive disorder. Brain Behav Immun. 2015;49:206-15. doi: 10.1016/j.bbi.2015.06.001
13. Sun Y, Wang D, Salvadore G, et al. The effects of interleukin-6 neutralizing antibodies on symptoms of depressed mood and anhedonia in patients with rheumatoid arthritis and multicentric Castleman's disease. Brain Behav Immun. 2017 Nov;66:156-64. doi: 10.1016/j.bbi.2017.06.014
14. Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry. 2016 Dec;21(12):1696-709. doi: 10.1038/mp.2016.3
15. Rybka J, Kedziora-Kornatowska K, Banas-Lezanska P, et al. Interplay between the pro-oxidant and antioxidant systems and proinflammatory cytokine levels, in relation to iron metabolism and the erythron in depression. Free Radic Biol Med. 2013;63:187-94. doi: 10.1016/j.freeradbiomed.2013.05.019
16. Norheim KB, Jonsson G, Omdal R. Biological mechanisms of chronic fatigue. Rheumatology. 2011;50:1009-18. doi: 10.1093/rheumatology/keq454
17. Ohsugi Y. Recent Advances in Immunopathophysiology of Interleukin-6: An Innovative Therapeutic Drug, Tocilizumab (Recombinant Humanized Anti-human Interleukin-6 Receptor Antibody), Unveils The Mysterious Etiology of Immune-Mediated Inflammatory Diseases. Biol Pharm Bull. 2007;30(11):2001-6. doi: 10.1248/bpb.30.2001
18. Rosenblat JD, Gregory JM, Carvalho AF, McIntyre RS. Depression and Disturbed Bone Metabolism: A Narrative Review of the Epidemiological Findings and Postulated Mechanisms. Curr Mol Med. 2016;16(2):165-78. doi: 10.2174/1566524016666160126144303
19. Kwack MH, Ahn JS, Kim MK, et al. Dihydrotestosterone-Inducible IL-6 Inhibits Elongation of Human Hair Shafts by Suppressing Matrix Cell Proliferation and Promotes Regression of Hair Follicles in Mice. J Investigat Dermatol. 2012;132:43-9. doi: 10.1038/jid.2011.274
20. Maes M, Anderson G, Kubera M, Berk M. Targeting classical IL-6 signalling or IL-6 trans-signalling in depression? Expert Opin Ther Targ. 2014;18(5):495-512. doi: 10.1517/14728222.2014.888417
21. Khandaker GM, Dantzer R, Jones PB. Immunopsychiatry: important facts. Psychol Med. 2017;47:2229-37. doi: 10.1017/S0033291717000745
22. Haapakoski R, Ebmeier KP, Alenius H, Kivimä ki M. Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances. Progr Neuro- Psychopharmacol Biol Psychiatr. 2016;66:63-72. doi: 10.1016/j.pnpbp.2015.11.012
23. Nikolaus S, Bode C, Taal E, van de Laar MA. Fatigue and factors related to fatigue in rheumatoid arthritis: a systematic review. Arthritis Care Res. 2013;65:1128-46. doi: 10.1002/acr.21949
24. Smolen JS, Beaulieu A, Rubbert-Roth A, et al; OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a doubleblind, placebo-controlled, randomised trial. Lancet. 2008;371:987-97. doi: 10.1016/S0140-6736(08)60453-5
25. Burmester GR, Feist E, Kellner H, et al. Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab after 4 and 24 weeks in patients with active rheumatoid arthritis: the first phase IIIb real-life study (TAMARA). Ann Rheum Dis. 2011;70:755-9. doi: 10.1136/ard.2010.139725
26. Strand V, Kosinski M, Chen C-I, et al. Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial. Arthritis Res Ther. 2016;18:198. doi: 10.1186/s13075-016-1096-9
27. Aletaha D, Bingham CO 3rd, Tanaka Y, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel group, multinational, phase 3 study. Lancet. 2017;389:1206-17. doi: 10.1016/S0140-6736(17)30401-4
28. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and Pain Comorbidity: A Literature Review. Arch Intern Med. 2003;163(20):2433-45. doi: 10.1001/archinte.163.20.2433
29. Kremer JM, Blanco R, Brzosko M, et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum. 2011;63:609-21. doi: 10.1002/art.30158
30. Jones G, Sebba A, Gu J, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010;69:88-96. doi: 10.1136/ard.2008.105197
31. Smith RS. The macrophage theory of depression. Med Hypotheses 1991;35:298-306. doi: 10.1016/0306-9877(91)90272-Z
32. Maes M, Scharpe S, Meltzer HY, et al. Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res. 1993;49:11-27. doi: 10.1016/0165-1781(93)90027-E
33. Gimeno D, Kivimä ki M, Brunner EJ, et al. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med. 2009 Mar;39(3):413-23. doi: 10.1017/S0033291708003723
34. Rothaug M, Becker-Pauly C, Rose-John S. The role of interleukin- 6 signaling in nervous tissue. Biochim Biophys Acta. 2016;1863:1218-27. doi: 10.1016/j.bbamcr.2016.03.018
35. Modrego PJ, Ferrandez J. Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type. A prospective cohort study. Arch Neurol. 2004;61:1290-3. doi: 10.1001/archneur.61.8.1290
36. Baune BT, Ponath G, Rothermundt M, et al. Association between cytokines and cerebral MRI changes in the aging brain. J Geriatr Psychiatry Neurol. 2009;22(1):23-34. doi: 10.1177/0891988708328216
37. Sharma AN, da Costa e Silva BF, Soares JC, et al. Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies. J Affect Disord. 2016 June;197:9-20. doi: 10.1016/j.jad.2016.02.067
38. Audet MC, Anisman H. Interplay between pro-inflammatory cytokines and growth factors in depressive illnesses. Front Cell Neurosci. 2013;7:68. doi: 10.3389/fncel.2013.00068
39. Haroon E, Raison CL, Miller AH. Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior. Neuropsychopharmacol Rev. 2012;37:137-62. doi: 10.1038/npp.2011.205
40. Pedard M, Demougeot C, Prati C, Marie C. Brain-derived neurotrophic factor in adjuvant-induced arthritis in rats. Relationship with inflammation and endothelial dysfunction. Prog Neuropsychopharmacol Biol Psychiatry. 2018;82:249-54. doi: 10.1016/j.pnpbp.2017.11.006
41. Khandaker GM, Pearson RM, Zammit S, et al. Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitudinal study. JAMA Psychiatry. 2014;71:1121-8. doi: 10.1001/jamapsychiatry.2014.1332
42. Stojanovich L, Marisavljevich D. Stress as a trigger of autoimmune disease. Autoimmun Rev. 2008 Jan;7(3):209-13. doi: 10.1016/j.autrev.2007.11.007
43. Prete C, Briano F, Pizzorni C, et al. Stress response system and personality in rheumatoid arthritis patients. Reumatismo. 2001;53(3):204-9. doi: 10.4081/reumatismo.2001.204
44. Slavich GM, Irwin MR. From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression. Psychol Bull. 2014 May;140(3):774-815. doi: 10.1037/a0035302
45. Bluthe RM, Dantzer R, Kelley KW. Effects of interleukin-1 receptor antagonist on the behavioral effects of lipopolysaccharide in rat. Brain Res. 1992:573:318-20. doi: 10.1016/0006-8993(92)90779-9
46. Yirmiya R. Endotoxin produces a depressive-like episode in rats. Brain Res. 1996;711:163-74. doi: 10.1016/0006-8993(95)01415-2
47. Mutlu O, Gumuslu E, Ulak G, et al. Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice. Life Sci. 2012;91:1252-62. doi: 10.1016/j.lfs.2012.09.023
48. Farooq RK, Isingrini E, Tanti A, et al. Is unpredictable chronic mild stress (UCMS) a reliable model to study depression-induced neuroinflammation? Behav Brain Res. 2012;231:130-7. doi: 10.1016/j.bbr.2012.03.020
49. Monje FJ, Cabatic M, Divisch I, et al. Constant darkness induces IL-6-dependent depression-like behavior through the NF-kappaB signaling pathway. J Neurosci. 2011;31:9075-83. doi: 10.1523/JNEUROSCI.1537-11.2011
50. Anisman H. Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci. 2009;34 (1):4-20.
51. Pfau ML, Russo SJ. Peripheral and central mechanisms of stress resilience. Neurobiol Stress. 2015;1:66-79. doi: 10.1016/j.ynstr.2014.09.004
52. Fagundes CP, Glaser R, Kiecolt-Glaser JK. Stressful early life experiences and immune dysregulation across the lifespan. Brain Behav Immun. 2013;27:8-12. doi: 10.1016/j.bbi.2012.06.014
53. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. Am J Prevent Med. 1998;14(4):245-58. doi: 10.1016/S0749-3797(98)00017-8
54. Danese A, Pariante CM, Caspi A, et al. Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci USA. 2007 Jan 23;104(4):1319-24. doi: 10.1073/pnas.0610362104
55. Carpenter LL, Gawuga CE, Tyrka AR, et al. Association between plasma IL-6 response to acute stress and early-life adversity in healthy adults. Neuropsychopharmacology. 2010 Dec;35(13):2617-23. doi: 10.1038/npp.2010.159
56. Miller GE, Cole SW. Сlustering of depression and inflammation in adolescents previously exposed to childhood adversity. Biol Psychiatry. 2012 July 1;72(1):34-40. doi: 10.1016/j.biopsych.2012.02.034
57. De Punder K, Entringer S, Heim C, et al. Inflammatory Measures in Depressed Patients With and Without a History of Adverse Childhood Experiences. Front Psychiatry. 2018;9:610. doi: 10.3389/fpsyt.2018.00610
58. Spitzer C, Wegert S, Wollenhaupt J, et al. Gender-specific association between childhood trauma and rheumatoid arthritis: A casecontrol study. J Psychosomat Res. 2013;74:296-300. doi: 10.1016/j.jpsychores.2012.10.007
59. Дрождина ЕН, Ковалевская ОБ, Серавина ОФ и др. Роль пси- хотравмирующих факторов в дезадаптации детей и подростков, страдающих ювенильным артритом. Социальная и клиническая психиатрия. 2012;22(1):44-50 [Drozhdina EN, Kovalevskaya OB, Seravina OF, et al. The role of traumatic factors in maladaptation of children and adolescents suffering from juvenile arthritis. Sotsial'naya i Klinicheskaya Psikhiatriya. 2012;22(1):44-50 (In Russ.)].
60. Sluzewska A, Rybakowski JK, Laciak M, et al. Interleukin-6 serum levels in depressed patients before and after treatment with fluoxetine. Ann NY Acad Sci. 1995;762:474-6. doi: 10.1111/j.1749-6632.1995.tb32372.x
61. Frommberger UH, Bauer J, Haselbauer P, et al. Interleukin-6- (IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci. 1997;247:228-33. doi: 10.1007/BF02900219
62. Xia Z, DePierre JW, Nassberger L. Tricyclic antidepressants inhibit IL-6, IL1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells. Immunopharmacology. 1996;34:27-37. doi: 10.1016/0162-3109(96)00111-7
63. Vogelzangs N, Duivis HE, Beekman AT, et al. Association of depressive disorders, depression characteristics and antidepressant medication with inflammation. Transl Psychiatry. 2012;2:e79. doi: 10.1038/tp.2012.8
64. Cattaneo A, Gennarelli M, Uher R, et al. Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline 'predictors' and longitudinal 'targets'. Neuropsychopharmacology. 2013;38:377-85. doi: 10.1038/npp.2012.191
65. Hiles SA, Baker AL, de Malmanche T, Attia J. Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis. Psychol Med. 2012;42:2015-26. doi: 10.1017/S0033291712000128
66. Hannestad J, DellaGioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology. 2011;36:2452-9. doi: 10.1038/npp.2011.132
67. Hashioka S. Antidepressants and neuroinflammation: can antidepressants calm glial rage down? Mini Rev Med Chem. 2011;11:555-64. doi: 10.2174/138955711795906888
68. Manikowska K, Mikolajczyk M, Mikolajczak P, Bobkiewicz- Kozlowska T. The influence of mianserin on TNF-α, IL-6 and IL-10 serum levels in rats under chronic mild stress. Pharmacological Rep. 2014;66:22-7. doi: 10.1016/j.pharep.2013.06.003
69. Kubera M, Kenis G, Bosmans E, et al. Stimulatory effect of antidepressants on the production of IL-6. Int Immunopharmacol. 2004;4:185-92. doi: 10.1016/j.intimp.2003.11.006
70. Fornaro M, Martino M, Battaglia F, et al. Increase in IL-6 levels among major depressive disorder patients after a 6-week treatment with duloxetine 60 mg/day: a preliminary observation. Neuropsychiatr Dis Treat. 2011;7:51-6. doi: 10.2147/NDT.S16382
71. Maes M, Bosmans E, de Jongh R, et al. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine. 1997;9:853-8. doi: 10.1006/cyto.1997.0238
72. Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 2000;22:370-9. doi: 10.1016/S0893-133X(99)00134-7
73. O'Brien SM, Scully P, Fitzgerald P, et al. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res. 2007;41:326-31. doi: 10.1016/j.jpsychires.2006.05.013
74. Harley J, Luty S, Carter J, et al. Elevated C-reactive protein in depression: a predictor of good long-term outcome with antidepressants and poor outcome with psychotherapy. J Psychopharmacol. 2010;24:625-6. doi: 10.1177/0269881109102770
75. Raison CL, Rutherford RE, Woolwine BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013;70(1):31-41. doi: 10.1001/2013.jamapsychiatry.4
76. Sukoff Rizzo SJ, Neal SJ, Hughes ZA, et al. Evidence for sustained elevation of IL-6 in the CNS as a key contributor of depressive- like phenotypes. Transl Psychiatry. 2012;2:e199. doi: 10.1038/tp.2012.120
77. Walker AJ, Foley BM, Sutor SL, et al. Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance. Behav Brain Res. 2015;293:198-202. doi: 10.1016/j.bbr.2015.07.026
78. De Kock M, Loix S, Lavand'homme P. Ketamine and peripheral inflammation. CNS Neurosci Ther. 2013;19:403-10. doi: 10.1111/cns.12104
79. Strand V, Reaney M, Chen C-I, et al. Sarilumab improves patientreported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors. RMD Open. 2017;3:e000416. doi: 10.1136/rmdopen-2016-000416
80. Smolen JS, Weinblatt ME, Sheng S, et al. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis. 2014;73:1616-25. doi: 10.1136/annrheumdis-2013-205137
81. Szepietowski JC, Nilganuwong S, Wozniacka A, et al. Phase I, randomized, double-blind, placebo-controlled, multiple intravenous, dose-ascending study of sirukumab in cutaneous or systemic lupus erythematosus. Arthritis Rheum. 2013;65(10):2661-71. doi: 10.1002/art.38091
82. Matcham F, James G, Hotopf M, et al. The impact of targeted rheumatoid arthritis pharmacological treatment on mental health: a systematic review and network meta-analysis. Arthritis Rheum. 2018;70(9):1377-91. doi: 10.1002/art.40565
83. Brietzke E, Scheinberg M, Lafer B. Therapeutic potential of interleukin- 6 antagonism in bipolar disorder. Med Hypoth. 2011;76(1):21-3. doi: 10.1016/j.mehy.2010.08.021
84. Zhou AJ, Lee Y, Salvadore G, et al. Sirukumab: A Potential Treatment for Mood Disorders? Adv Ther. 2017;34:78-90. doi: 10.1007/s12325-016-0455-x
85. Miller BJ, Dias JK, Lemos HP, Buckley PF. An open-label, pilot trial of adjunctive tocilizumab in schizophrenia. J Clin Psychiatry. 2016;77:275-6. doi: 10.4088/JCP.15l09920
86. Miller BJ, Buckley PF. Monoclonal antibody immunotherapy in psychiatric disorders. Lancet Psychiatry. 2017;4(1):13-5. doi: 10.1016/S2215-0366(16)30366-2
87. Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest. 2011;121(9):3375-83. doi: 10.1172/JCI57158
88. Waetzig GH, Rose-John S. Hitting a complex target: an update on interleukin6 trans-signalling. Expert Opin Ther Targets. 2012;16(2):225-36. doi: 10.1517/14728222.2012.660307
89. Garbers C, Thaiss W, Jones GW, et al. Inhibition of classic signaling is a novel function of soluble glycoprotein 130 (sgp130), which is controlled by the ratio of interleukin 6 and soluble interleukin 6 receptor. J Biol Chem. 2011;286:42959-70. doi: 10.1074/jbc.M111.295758
Рецензия
Для цитирования:
Лисицына Т.А., Вельтищев Д.Ю., Лила А.М., Насонов Е.Л. Интерлейкин 6 как патогенетический фактор, опосредующий формирование клинических проявлений, и мишень для терапии ревматических заболеваний и депрессивных расстройств. Научно-практическая ревматология. 2019;57(3):318-327. https://doi.org/10.14412/1995-4484-2019-318-327
For citation:
Lisitsyna T.A., Veltishchev D.Yu., Lila A.M., Nasonov E.L. Interleukin 6 as a pathogenic factor mediating clinical manifestations and a therapeutic target for rheumatic diseases and depressive disorders. Rheumatology Science and Practice. 2019;57(3):318-327. (In Russ.) https://doi.org/10.14412/1995-4484-2019-318-327