Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis

Treatment with a chimeric mAb to TNF-alpha has been shown to suppress infla mmation and improve patient well-being in rheumatoid arthritis (ICS), but t he mechanisms of action of such treatment have not been fully explored. Her e we show that in vivo administration of anti-TNF-alpha Ab, using a longitu dinal analysis, results in the rapid down-regulation of a spectrum of cytok ines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variati on in the serum levels of some of these were detected. These results were c onsistent with the concept of a cytokine-dependent cytokine cascade, and th e degree of clinical benefit noted after anti-TNF-alpha therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-alph a, such as IL-6, which reached normal levels within 24 h. Serum levels of c ytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL- 1 receptor antagonist, Reductions in acute-phase proteins occurred after se rum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. Th e latter reduction could be of importance, as it is a risk factor for ather osclerosis, which is augmented in RA patients.