Risk of infection during treatment with tumor necrosis factor-α inhibitors

Tumor necrosis factor-alpha (TNF) is essential for immune defense. TNF plays a major role in the recruitment of inflammatory cells to the site of infection and in the formation and maintenance of granulomas. In addition, it plays a primary and detrimental role in chronic autoimmune diseases. Drugs that inhibit TNF are effective in the treatment of inflammatory rheumatic and autoimmune diseases. However, the three currently available TNF antagonists (etanercept, infliximab and adalimumab) decrease host resistance to granulomatous diseases such as tuberculosis. The incidence of tuberculosis in patients treated with TNF antagonists is higher than in the general population. There are a number of case reports describing the association of TNF-antagonists and the presentation of other infectious diseases such as histoplasmosis, listeriosis, coccidioidomycosis, candidiasis and aspergillosis. These case reports, however, are anecdotal. Nonetheless, patients treated with TNF antagonists are immunocompromised and infectious diseases are most likely more frequent and may present differently than expected. In this review, we describe the role of TNF in constraining infectious diseases, the difference between the three available TNF antagonists, and we discuss the relevant clinical data published in the literature as related to the risk of anti-TNF therapy for infectious diseases.