Interleukin-12: role of interferon-gamma in IL-12 adverse effects.
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.
Ryffel
B
B
Institute of Pathology, Basel, Switzerland.
D000740:Anemia / Q000139:chemically induced; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D004361:Drug Tolerance; D006529:Hepatomegaly / Q000139:chemically induced; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology / Q000633:toxicity; D018664:Interleukin-12 / Q000009:adverse effects / Q000494:pharmacology; D051379:Mice; D011654:Pulmonary Edema / Q000139:chemically induced; D017471:Receptors, Interferon / Q000172:deficiency; D012453:Saimiri; D013163:Splenomegaly / Q000139:chemically induced; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D018664:Interleukin-12; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor