[Cytokines in rheumatoid arthritis].

In this review we have examined the role of a variety cytokines in the pathogenesis of rheumatoid arthritis (RA) and their possible applications in the treatment of this disease. Cytokines are small protein molecules, released by activated cells which function as chemical messengers between cells of the immune, inflammatory and other systems. The studies using isolated cells from RA synovial membranes indicate that the vast majority of known cytokines are found in RA synovial tissue. These include IL-1, TNF alpha, IL-6, IL-8, TGF beta, GM-CSF and others. TNF alpha and IL-1 are important, "pivotal" molecules in the disease process. TNF alpha has been detected in the serum and synovial fluid of patients with RA, suggesting an important contribution of this cytokine to the development of arthritis. Clinically, TNF-alpha has been also associated with markers of rheumatoid disease activity. Rheumatoid synovial tissue synthesizes large amounts of both forms of IL-1 (IL-1 alpha and IL-1 beta) in vitro. IL-1 can exert a variety of systemic effects, including induction of fever and synthesis of acute phase proteins. It also induces local joint effects mediating production of fibroblast fibronectin and tissue collagenase. IL-6 is found in greater quantities in the synovial fluids from patients with RA compared to osteoarthritis. Synovial fluid IL-6 levels correlate with local IgM rheumatoid factor and systemic acute phase protein production. Chemokines, including IL-8, have potent chemotactic activity for cells of the immune system. IL-8 not only participates in the inflammatory phase of RA, but also participates in the vasculoproliferative phase of this disease. Recent data on the cytokine profile in RA implies that alternative treatment strategies should be considered. Potential approaches for modifying the cytokine network include inhibition of cytokine production or their action, inhibition of signal transduction and administration of suppressive cytokines.