ROLE OF CYTOKINES, ACUTE-PHASE PROTEINS, AND CHEMOKINES IN THE PROGRESSION OF RHEUMATOID-ARTHRITIS

Rheumatoid arthritis (RA) has no firm etiologic basis. It progresses a s an autoimmune disease and evolves into a chronic inflammatory joint disease complicated by recurrent episodes of systemic acute-phase reac tions, which sometimes result in amyloidosis. Cytokines play a pivotol role in inflammation and the immune response, Proinflammatory cytokin es such as interleukin-1, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 are present at high levels in arthritic joints, and the ir blood concentration correlates with the severity of the RA. Some of the activities of the proinflammatory cytokines, such as stimulation of leukocyte infiltration and release of their proteolytic enzymes, ma y be mediated by acute phase proteins (APPs), such as C-reactive prote in and serum amyloid A, and by chemokines such as interleukin-8. Cytok ines, chemokines, and APPs reciprocally regulate each others' expressi on and activities, constituting a communication network between fibrob lasts, macrophages, lymphocytes, and hepatocytes. Activation of the ne twork results in inflammation and the progressive destruction of joint s and systemic symptoms characteristic of RA.