Serious Infections Associated with Anticytokine Therapies in the Rheumatic Diseases

Abstract

The ability to target and neutralize macrophage-derived inflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), has emerged in recent years as one of the most important advances in the treatment of rheumatoid arthritis, Crohn's disease, and several other systemic inflammatory diseases. In rheumatoid arthritis, for example, these biological agents rapidly reduce signs and symptoms of joint inflammation and profoundly slow the progression of joint damage. However, data that have emerged following Food and Drug Administration approval of these agents have alerted clinicians to an increased likelihood of opportunistic infections in patients treated with these agents, particularly tuberculosis. The effect of TNF inhibition on the frequency of infection with more common bacterial pathogens is less clear. Animal models of tuberculosis and other opportunistic infections have demonstrated the importance of TNF-alpha in controlling and containing intracellular pathogens. The spectrum of infections reported to date in the setting of anti-TNF-alpha treatment is reviewed here. In addition, relevant animal data illustrating potential mechanistic roles for TNF-alpha in host responses to infection are also reviewed.