Targets of anticytokine therapy and the risk of infections in humans and mice.
OBJECTIVE
To examine the type and risk of infections in humans and mice deficient in proinflammatory cytokines. Naturally occurring or manipulated genetic defects of tumor necrosis factor, interleukins-1, -6, -12, and -15, and interferon-gamma are examined for their increased susceptibility to, or protection from, infection.


RESULTS
Interleukin-12p40 and interferon-gamma-blockers may lead to increased incidence of infections with intracellular bacteria, parasites, and fungi. In addition, we may see viral infections with interferon-gamma-blockers. Increased risk of infections is unlikely with either interleukin-1- or interleukin-15-blockers. Interleukin-6-blockers may lead to increased risk of infection with extracellular bacteria, viruses, parasites and fungi.


CONCLUSIONS
In tumor necrosis factor knockout mice, increased susceptibility to pathogens are reported that are normally controlled by granuloma formation. In patients treated with tumor necrosis factor-blockers, a two-fold increase of granulomatous infections, predominantly reactivation of latent tuberculosis, is found. The infections detected in tumor necrosis factor knockout mice were accurate for predicting the infections observed when using tumor necrosis factor-blockers. If a similar correlation exists for other cytokines, the use of interferon-gamma and interleukin-12p40 blockers, and possibly interleukin-6 blockers, will lead to an increased risk for severe infections. Care should be taken when new cytokine blockers/antagonists are introduced.
van de Vosse
Esther
E
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands. E.van_de_Vosse@LUMC.nl
van Agtmael
Michiel A
MA
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000187:drug effects; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007239:Infections / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy; D007372:Interferons / Q000037:antagonists & inhibitors / Q000187:drug effects; D007378:Interleukins / Q000037:antagonists & inhibitors; D051379:Mice; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha
D016207:Cytokines; D007166:Immunosuppressive Agents; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons