INFLAMMATION AND IMMUNITY: A ROLE OF PATHOGENESIS OF OSTEOARTHRITIS

In this review we analyze literature data concerning participation of synovial inflammation, subchondral bone, humoral and cellular immune responses towards various cartilage autoantigens in the initiation and progression of primary osteoarthritis (OA). The vast majority of studies showed that the synovial inaflammation in OA is less pronounced than in RA but is more pronounced than in healthy people. In OA synovial tissue, macrophages and T-cells predominate in the inflammatory infiltrate. Some authors detected mast cells in the OA synovium in quantities higher than in healthy control and significantly higher than in RA patients. Most of researchers found many cytokines related to innate and adaptive immune cells in the OA synovial tissue, while in some studies the cells producing those cytokines were not identified. Among the cytokines there were both pro-inflammatory and anti-inflammatory ones: IL-1b, TNFα, IFNγ, IL-4, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18. In addition, some authors detected IL-5, IL-13, IL-19, IL-21, IL-26, IL-32, and TGFb. A role of adaptive immune response in OA is supported by the presence of autoantibodies against antigen determinants of collagens type II, IX, XI, aggrecan, fibronectin fragments, in the synovial tissue, synovium fluid, and peripheral blood serum. The research data clearly support a role of chronic inflammation and changes in innate and adaptive immune response in the pathogenesis of OA thus justifying the change of the disease name from “osteoarthrosis” to “osteoarthritis”. This novel understanding of OA pathogenesis is paramount as it provides a rationale for modern anti-inflammatory treatments and discovery of new therapeutic targets. We discuss the results of studies evaluating efficacy and safety of some types of anti-inflammatory treatment of OA. Until now, treatment of OA directed on inflammation control was not successful. Thus, clinical trials of anti-TNFα anti-IL-1b strategies for the treatment of OA did not show clinically significant improvement in spite of multiple studies demonstrating elevated concentrations of TNFα and IL-1bin synovial fluid and subchondral bone in OA thus suggesting the role of these cytokines in the OA pathogenesis. On the other side, treatment with IL-1 inhibitor diacerein was found to be effective which can be explained by pleiotropic effects of this drug. It should be stressed out that in order to increase the efficacy of anti-inflammatory treatments of OA they should be initiated at early disease stages, thus necessitating the use of new informative biormarkers of early OA.

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