Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis.
This review has summarized some of the evidence suggesting that cytokines may play an important role in mediating pathophysiologic events in RA. However, these proteins are capable of mediating both stimulatory (agonist) and inhibitory (antagonist) effects in the rheumatoid synovium. GM-CSF, IL-1, TNF alpha, and PDGF are all produced in the rheumatoid synovium and may function to induce inflammation, enzyme release, fibroblast proliferation, and tissue destruction. Local release of IL-6 may alter the effects of IL-1 and TNF alpha, as well as induce Ig production and hepatic synthesis of acute-phase proteins. However, specific inhibitors of IL-1 and TNF alpha exist, which, if also released into the synovium, may antagonize the proinflammatory effects of these cytokines. In addition, IL-1 may have antiinflammatory effects, such as the induction of the synthesis of collagen and enzyme inhibitors by chondrocytes and synovial fibroblasts. Stimulation of these latter cells by TGF beta also may result in decreased matrix degradation and increased formation of scar tissue. The developing scenario is one of cell-cell interactions that are influenced in positive and negative manners by the local release of various mediators. A further understanding of cytokines and cytokine inhibitors in the rheumatoid synovium may lead to the development of more specific and effective therapeutic agents.
Arend
W P
WP
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Dayer
J M
JM
D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D001685:Biological Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D016207:Cytokines; D006801:Humans
D001685:Biological Factors; D016207:Cytokines