PROSPECTS FOR USING TOCILIZUMAB IN SYSTEMIC SCLEROSIS
https://doi.org/10.14412/1995-4484-2015-632-640
Abstract
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 pathological
conditions. 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.
About the Author
L. P. Ananyeva
V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia 34A, Kashirskoe Shosse, Moscow 115522
Russian Federation
Russian Federation
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Ananyeva L.P. PROSPECTS FOR USING TOCILIZUMAB IN SYSTEMIC SCLEROSIS. Rheumatology Science and Practice. 2015;53(6):632-640. (In Russ.) https://doi.org/10.14412/1995-4484-2015-632-640
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