Can SOCS make arthritis better?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by autoimmunity and infiltration of joint synovium by activated inflammatory cells, including neutrophils, macrophages, lymphocytes, plasma cells, and osteoclasts (reviewed in ref. 1). Morbidity in RA occurs secondary to the destruction of cartilage and bone by an inflammatory mass termed the pannus, which consists predominantly of activated macrophages and proliferating synovial fibroblasts. Synovial inflammation is regulated by cytokines (1). Pro-inflammatory cytokines implicated in RA pathogenesis include TNF-α, IL-1, IL-6, IL-12, IL-15, IL-18, IFN-γ, and GM-CSF. A key role for TNF-α and IL-1 in RA pathogenesis has been confirmed by the success of TNF and IL-1 neutralization in the treatment of RA. RA synovium is also characterized by the expression of anti-inflammatory cytokines and cytokine antagonists, including TGF-β, IL-10, the IL-1 receptor antagonist, and soluble TNF receptors. Production of these factors reflects an attempt to control inflammation and achieve homeostasis. The idea that the balance between pro- and anti-inflammatory factors is important in regulating the rate of progression, and thus the eventual severity and morbidity, of RA has gained broad acceptance among RA researchers (1).