New areas of the pharmacotherapy of rheumatic diseases are inhibition of interleukin-6 and interleukin-17

Abstract

Significant progress related particular to the use of interleukin (IL)-6 and IL17 inhibitors has been made in the pharmacotherapy of rheumatic diseases. IL-6 is a cytokine that has a wide range of biological activity and affects different types of cells. There is evidence for the important role of IL-6 hyperproduction not only in rheumatoid arthritis (RA), but also in other immune inflammatory rheumatic diseases (systemic lupus erythematosus (SLE), scleroderma system atica, idiopathic inflammatory myopathies, giant cell arteritis, etc.). IL-6 inhibition primarily with humanized monoclonal antibodies against IL-6 receptors (tocilizumab – TCZ)) is considered as one of the promising areas of pharmacotherapy for these diseases. The successful results of TCZ use have created pre requisites for the design of other medicaments that can form a novel class of IL-6 inhibitors, genetically engineered biological agents, in the future. There is another new area in the treatment of immune inflammatory rheumatic diseases, which is the inhibition of the cytokine IL17A that provides interaction between innate and acquired immunity and is synthesized by a wide range of immunocompetent cells, the socalled Th17 ones in particular. IL-17A is implicated in the immunopathogenesis of a broad spectrum of immune inflammatory diseases, including RA, psoriasis, psoriatic arthritis, inflammatory bowel diseases, SLE, allergic diseases, transplantation immunity, obesity, carcinogenesis, etc. Elevated IL-17A concentrations correlate with the activity and severity of a pathological process. The pathogenetic effects of IL-17 in RA may be associated with its involvement in the development of synovial inflammation and joint destruction. The therapeutic efficiency of inhibition of Th17 cells and IL-17A synthesis in autoimmune diseases was first indirectly demonstrated in psoriasis. This provided the basis for the elaboration of therapeutic approaches associated with the direct inhibition of IL-17 effects in these patients. Thus, the use of IL-6 inhibitors (primarily TCZ) and, probably, IL-17 will make significant progress in the treatment of not only RA, but other severe potentially deadly immune inflammatory rheumatic diseases in the future.