Cytokines in chronic inflammatory synovitis

Cytokines likely play a role in the pathogenesis of rheumatoid arthritis and other chronic inflammatory arthritidies. Recent studies on the cytokine profile of inflammatory synovitis have provided insight into the mechanisms of cellular activation in the inflamed joint. Although gamma interferon has been proposed as a major macrophage activating factor and inducer of class II major histocompatibility antigens in the joint, studies using sensitive and specific immunoassays have shown that the concentration of this lymphokine in synovial fluid is probably not sufficient to account for the high level of HLA-DR expression on Type A synoviocytes and macrophages in the joint. In contrast, GM-CSF has recently been identified in synovial effusions of patients with rheumatoid arthritis and is produced by synovial tissue cells in vitro. Like gamma interferon, GM-CSF is a known macrophage activating factor and induces HLA-DR on cells of macrophage lineage. Furthermore, supernatants of cultured synovial tissue cells contain an HLA-DR inducing factor that is neutralized by specific antibodies to GM-CSF but not by antibodies to gamma interferon. These data suggest that GM-CSF plays a significant role in macrophage activation in the synovium.