Korean J Med.  2009 Jan;76(1):1-6.

Updated Pathophysiology of rheumatoid arthritis

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

Abstract

Rheumatoid arthritis is a chronic inflammatory disease that primarily affects joint synovium. Although its etiology has yet to be identified, the underlying mechanism of joint inflammation is understood as autoimmune process. The inflamed synovium is thickened due to synovial hyperplasia and infiltrating mononuclear cells such as T and B lymphocytes, macrophages, and plasma cells. Key inflammatory cytokines TNF-alpha and IL-1, as shown by the significant therapeutic effect of their blockade, are mainly secreted by macrophages whereas IL-17 is secreted by a newly recognized subset of T cells (Th17 cells) and induces TNF-alpha and IL-1 production by adjacent macrophages, synoviocytes, and chondrocytes. IL-17 has also been shown to induce RANKL from osteoblasts, thereby indicating that this cytokine plays as an upstream molecule that regulates inflammation and osteoclastogenesis. More importantly, IL-17 has been shown to convert acute inflammation into chronic inflammation and when combined with already important cytokines, more marked inflammation occurs. The role of B cells as antigen presenting cells are now being recognized based on the therapeutic effect of rituximab, a B cell inhibitor, in rheumatoid arthritis. Great attention has been turned to anti-citrullinated peptide antibodies because they form immune complex and contribute to inflammation by activating complement system. Recently, clinical trials showed therapeutic efficacy of tocilizumab, monoclonal antibody against IL-6 receptor, suggesting relevant involvement of IL-6 in disease process of rheumatoid arthritis. Thus, various cellular and molecular players seem to interact within rheumatoid synovium to perpetuate inflammation. Further studies are needed to explore the exact mechanisms of development and maintenance of inflammation in rheumatoid arthritis.

Keyword

Rheumatoid arthritis; Synovium, and inflammation
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