Interleukin-12: role of interferon-gamma in IL-12 adverse effects

Clin Immunol Immunopathol. 1997 Apr;83(1):18-20. doi: 10.1006/clin.1996.4306.

Abstract

Interleukin 12 (IL-12) activates natural killer and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and therefore enhances a Th1- or cell-mediated immune response. The immunostimulatory property of IL-12 may be used clinically in cancer and viral diseases. Safety studies in rodents and primates demonstrated a rather small therapeutic window with hepato- and splenomegaly, myelodepression, and lung edema. Investigations in mutant mice deficient for the IFN-gamma receptor (IFN-gamma R-/-) revealed that both the biologic and toxic effects are indirect and largely due to IL-12-induced IFN-gamma. The significance of these findings for the safety in man needs to be explored.

MeSH terms

  • Anemia / chemically induced
  • Animals
  • Clinical Trials, Phase I as Topic
  • Drug Tolerance
  • Hepatomegaly / chemically induced
  • Humans
  • Interferon-gamma / physiology
  • Interferon-gamma / toxicity
  • Interleukin-12* / adverse effects
  • Interleukin-12* / pharmacology
  • Mice
  • Pulmonary Edema / chemically induced
  • Receptors, Interferon / deficiency
  • Saimiri
  • Splenomegaly / chemically induced

Substances

  • Receptors, Interferon
  • interferon gamma receptor
  • Interleukin-12
  • Interferon-gamma