Journal
RHEUMATOLOGY
Volume 51, Issue -, Pages V3-V11Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/kes113
Keywords
B cell; cytokine; interleukin-1; interleukin-6; interleukin-17; pathogenesis; pathophysiology; rheumatoid arthritis; T cell; tumour necrosis factor-alpha
Categories
Funding
- F. Hoffmann-La Roche Ltd.
- Roche
- Abbott Laboratories
- Allergan
- AstraZeneca
- Boehringer Ingelheim
- Chelsea Therapeutics
- Chugai Pharma
- Eli Lilly
- GlaxoSmithKline
- Jazz Pharmaceuticals
- Merrimack Pharmaceutical
- Merck Sharp Dohme
- Pfizer
- Pierre Fabre Medicament
- Schering Plough
- Synovate
- UCB
- Wyeth
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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 naive 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-alpha, 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.
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