Tumor-necrosis-factor blockers: differential effects on mycobacterial immunity.
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)- gamma 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- gamma .
Saliu
Oluwabunmi Y
OY
Department of Medicine, University of Medicine and Dentistry, New Jersey Medical School, Newark, USA.
Sofer
Carolina
C
Stein
Dana S
DS
Schwander
Stephan K
SK
Wallis
Robert S
RS
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000995:Antitubercular Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D000069285:Infliximab; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000995:Antitubercular Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept