References

rsp

Научно-практическая ревматология

Rheumatology Science and Practice

1995-44841995-4492

IMA-PRESS, LLC

10.14412/1995-4484-2015-632-640

rsp-2155

Research Article

ПРОГРЕСС В РЕВМАТОЛОГИИ В XXI ВЕКЕ

PROGRESS IN RHEUMATOLOGY IN THE XXI CENTURY

Перспективы применения тоцилизумаба при системной склеродермии

PROSPECTS FOR USING TOCILIZUMAB IN SYSTEMIC SCLEROSIS

Ананьева

Л. П.

Ananyeva

L. P.

ananieva@irramn.ru

ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия 115522 Москва, Каширское шоссе, 34АРоссияV.A. Nasonova Research Institute of Rheumatology, Moscow, Russia 34A, Kashirskoe Shosse, Moscow 115522Russian Federation

2015

05022016

536632640

2016

Ананьева Л.П.

Ananyeva L.P.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://rsp.mediar-press.net/rsp/article/view/2155

Интерлейкин 6 (ИЛ6) – один из ключевых цитокинов, участвующих в процессе воспаления и обладающий плейотропными свойствами. Разнообразные эффекты ИЛ6 осуществляются в результате передачи внутриклеточного сигнала двумя путями – через прямое связывание с мембранным рецептором с молекулярной массой 80 кДa («классический» путь) или вследствие абсорбирования комплекса ИЛ6 с его растворимым рецептором на другом трансмембранном рецепторе – gp130 (транссигнализация). Разные пути сигнализации вызывают различные последствия. Классический путь передачи сигнала активирует преимущественно протективные и регенеративные процессы, транссигнализация несет провоспалительный потенциал. В обзоре приведены схемы реализации сигнальных стимулов и показано, что ИЛ6 и его рецепторы представляют собой динамическую систему со сложно организованной регуляцией, позволяющей адаптироваться к стрессовым изменениям гомеостаза. Детально рассмотрены данные, свидетельствующие о влиянии ИЛ6 на развитие и поддержание ряда характерных для системной склеродермии (ССД) патогенетических нарушений, таких как активация эндотелия, развитие и поддержание воспаления и избыточное отложение компонентов экстрацеллюлярного матрикса в тканях. Активация эндотелиальных клеток в процессе транссигнализации приводит к усилению экспрессии молекул адгезии, высвобождению хемокинов и последующему выделению ИЛ6. Избыточная секреция ИЛ6 может инициировать фиброзирующий процесс и способствовать дальнейшему развитию патологических нарушений. При ССД имеют место аутоиммунные нарушения, теоретически связанные с гиперпродукцией ИЛ6. Повышение концентрации ИЛ6 в крови при ССД ассоциируется с клиническими параметрами заболевания – активностью, тяжестью, ухудшением прогноза и снижением выживаемости. В совокупности приведенные данные свидетельствуют о том, что блокирование ИЛ6 может иметь терапевтический потенциал при ССД. Приведены первые клинические данные об успешном применении блокатора рецепторов ИЛ6 тоцилизумаба для лечения ССД.

Interleukin 6 (IL-6) is one of the key cytokines that are involved in inflammation and that has pleiotropic properties. Diverse effects of IL-6 result from the transmission of an intracellular signal in two ways: via direct binding to a membrane receptor having a molecular mass of 80 kDA (a classical way) or absorption of the IL-6 complex with its soluble receptor on another transmembrane receptor – gp-130 (trans-signaling). Different signaling pathways lead to various consequences. The classical way of signal transmission activates mainly protective and regenerative processes; trans-signaling has a proinflammatory potential. The review gives schemes of signal stimuli and shows that IL-6 and its receptors are a dynamic intricately organized regulatory system that can adapt to stress-induced homeostatic changes. It considers in detail evidence suggesting the effect of IL-6 on the development and maintenance of a number of systemic sclerosis (SS)-specific pathogenetic disorders, such as the activation of the endothelium, the development and maintenance of inflammation, and excessive deposition of extracellular matrix components in tissues. Endothelial cell activation during trans-signaling gives rise to an enhanced adhesion molecule expression, chemokine release, and further production of IL-6. Excessive secretion of the latter may initiate a fibrosing process and favor the further development of pathologicalconditions. Autoimmune disorders theoretically associated with IL-6 overproduction occur in SS. Elevated blood IL-6 concentrations in SS are related to disease clinical parameters, such as activity, severity, worse prognosis, and reduced survival. Taken together, the data presented suggest that IL-6 blocking may have a therapeutic potential in SS. The first clinical data on successfully using the IL-6 receptor antagonist tocilizumab to treat SS are given.

системная склеродермиятоцилизумабцитокиныинтерлейкин 6

scleroderma systematicatocilizumabcytokinesinterleukin 6

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The authors declare that there are no conflicts of interest present.