Pathogenetic significance of the use of a humanized monoclonal antibody to the IL-6-α receptor (tocilizumab) in the treatment of immuno-inflammatory diseases

Abstract

The article discusses the participation of interleukin-6 (IL6) in the formation of pathogenetic mechanisms of immuno-inflammatory diseases (IID). IL6 is one of the central cytokine in progressive IID. The biological activity of IL6 is determined by its ability to activate target genes that regulate differentiation, apoptosis and proliferation of immunocompetent cells. The immune-inflammatory effects of IL6 include regulation of the acute phase reaction, differentiation of immune cells, switching from innate to adaptive type of immune response (activation of T-helper 17 (Th17) cells and T-follicular Th-cells, suppression of the formation of T-regulatory cells, synthesis antibodies by B cells), stimulation of hematopoiesis (maturation of myeloid progenitors and megakaryocytes, leading to neutrophilia and thrombocytosis), neoangiogenesis, osteoclast-mediated bone remodeling. Currently, the use of a humanized monoclonal antibody to the IL-6α receptor (tocilizumab) is one of the most promising directions in the treatment of rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, large arterial vasculitis – aortoarteritis, temporal arteritis. The use of tocilizumab is included in the draft recommendations for the treatment of IID in conditions of coronavirus disease 2019 (COVID-19) developed by the All-Russian public organization “Association of Rheumatologists of Russia”. The presented data from international and domestic studies, as well as our own clinical experience, suggest that Tocilizumab (Actemra) is a highly effective and safe genetic engineering biological drug (GEBD) in the treatment of IID, and its use leads to a decrease in clinical and immunological activity and helps to improve life prognosis both when appointing as a first-line GEBD therapy and in case of ineffectiveness of other biological drugs and basic anti-inflammatory drugs in this category of patients.