Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis.
RA is a progressive inflammatory autoimmune disease with articular and systemic effects. Its exact cause is unknown, but genetic and environmental factors are contributory. T cells, B cells and the orchestrated interaction of pro-inflammatory cytokines play key roles in the pathophysiology of RA. Differentiation of naïve T cells into Th 17 (T(H)17) cells results in the production of IL-17, a potent cytokine that promotes synovitis. B cells further the pathogenic process through antigen presentation and autoantibody and cytokine production. Joint damage begins at the synovial membrane, where the influx and/or local activation of mononuclear cells and the formation of new blood vessels cause synovitis. Pannus, the osteoclast-rich portion of the synovial membrane, destroys bone, whereas enzymes secreted by synoviocytes and chondrocytes degrade cartilage. Antigen-activated CD4(+) T cells amplify the immune response by stimulating other mononuclear cells, synovial fibroblasts, chondrocytes and osteoclasts. The release of cytokines, especially TNF-α, IL-6 and IL-1, causes synovial inflammation. In addition to their articular effects, pro-inflammatory cytokines promote the development of systemic effects, including production of acute-phase proteins (such as CRP), anaemia of chronic disease, cardiovascular disease and osteoporosis and affect the hypothalamic-pituitary-adrenal axis, resulting in fatigue and depression.
King's Musculoskeletal Clinical Trials Unit, King's College London, London, UK. choyeh@cardiff.ac.uk
Ernest
E
Choy
D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000503:physiopathology; D001402:B-Lymphocytes / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology
D016207:Cytokines