Tumor-Necrosis-Factor Blockers: Differential Effects on Mycobacterial Immunity

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Abstract

Background.

Tumor necrosis factor (TNF) plays a pathogenic role in rheumatoid arthritis but is essential for antimycobacterial host defenses. The risk of reactivation of latent Mycobacterium tuberculosis infection is greater with the TNF monoclonal antibody infliximab than with the soluble TNF receptor etanercept. The basis of this difference is not known

Methods.

The effects that the monoclonal antibodies infliximab and adalimumab and the receptor etanercept have on antimycobacterial immune functions were studied by use of therapeutic drug concentrations in whole-blood culture

Results.

Infliximab and adalimumab reduced the proportion of tuberculosis-responsive (CD69+) CD4 cells by 70% and 49%, respectively (P<.05), and suppressed antigen-induced interferon (IFN)—γ production by 70% and 64% (P<.05), respectively; in contrast, etanercept produced no significant effect. Interleukin-10 production was equally suppressed by all 3 drugs. Adalimumab and etanercept had divergent, concentration-dependent effects on control of intracellular growth of M. tuberculosis. None of the drugs induced significant levels of apoptosis or necrosis, in either monocytes or T cells

Conclusions.

The tuberculosis risk posed by infliximab may reflect its combined effects on TNF and IFN-γ

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