TY - JOUR
T1 - Targets of anticytokine therapy and the risk of infections in humans and mice
AU - Van De Vosse, Esther
AU - Van Agtmael, Michiel A.
PY - 2007/11
Y1 - 2007/11
N2 - PURPOSE OF REVIEW: 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-γ are examined for their increased susceptibility to, or protection from, infection. RECENT FINDINGS: Interleukin-12p40 and interferon-γ-blockers may lead to increased incidence of infections with intracellular bacteria, parasites, and fungi. In addition, we may see viral infections with interferon-γ-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. SUMMARY: 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-γ 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.
AB - PURPOSE OF REVIEW: 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-γ are examined for their increased susceptibility to, or protection from, infection. RECENT FINDINGS: Interleukin-12p40 and interferon-γ-blockers may lead to increased incidence of infections with intracellular bacteria, parasites, and fungi. In addition, we may see viral infections with interferon-γ-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. SUMMARY: 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-γ 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.
KW - Deficiency
KW - Interferons
KW - Interleukins
KW - Knockout
KW - Mice
KW - Tumor necrosis factor-alpha
UR - http://www.scopus.com/inward/record.url?scp=34948886115&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/BOR.0b013e3282f05c6d
DO - https://doi.org/10.1097/BOR.0b013e3282f05c6d
M3 - Review article
C2 - 17917545
SN - 1040-8711
VL - 19
SP - 626
EP - 635
JO - Current Opinion in Rheumatology
JF - Current Opinion in Rheumatology
IS - 6
ER -