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

TLDR

Treatment with a chimeric anti‑TNF‑α monoclonal antibody suppresses inflammation and improves well‑being in rheumatoid arthritis, yet its precise mechanisms remain incompletely understood. Longitudinal analysis shows that anti‑TNF‑α therapy rapidly down‑regulates a broad spectrum of cytokines, cytokine inhibitors, and acute‑phase proteins—including IL‑6, soluble TNFRs, and serum amyloid A—within 24 h, supporting a cytokine‑dependent cascade that may also reduce atherosclerotic risk.

Abstract

Treatment with a chimeric mAb to TNF-alpha has been shown to suppress inflammation and improve patient well-being in rheumatoid arthritis (RA), but the mechanisms of action of such treatment have not been fully explored. Here we show that in vivo administration of anti-TNF-alpha Ab, using a longitudinal analysis, results in the rapid down-regulation of a spectrum of cytokines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variation in the serum levels of some of these were detected. These results were consistent with the concept of a cytokine-dependent cytokine cascade, and the degree of clinical benefit noted after anti-TNF-alpha therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-alpha, such as IL-6, which reached normal levels within 24 h. Serum levels of cytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL-1 receptor antagonist. Reductions in acute-phase proteins occurred after serum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. The latter reduction could be of importance, as it is a risk factor for atherosclerosis, which is augmented in RA patients.