IL-12: for better and for worse

Interleukin 12 (IL-12) has gained more attention when it was discovered to be crucial in directing the immune response towards a type 1 response that appeared to be protective in a Leishmania–mouse model. The protective immunity against other intracellular parasites such as Toxoplasma gondii was also associated with type-1 immune responsiveness. In order to reveal the parasite antigen that could trigger IL-12 production by macrophages, it was found that live Toxoplasma or a lysate prepared from Toxoplasma tachyzoites induced secretion of the bioactive IL-12 p70 heterodimer [Schade, B. and Fischer, H-G. (2001) Vet. Parasitol. 100, 63–74]. Surprisingly, when using macrophages from different inbred mouse strains, cells from T. gondii-susceptible mice released more IL-12 following Toxoplasma challenge than those in resistant mice. Furthermore, Toxoplasma isolates that were virulent in mice became less efficient IL-12 inducers after attenuation. These results suggest that, although IL-12 induction is crucial for protective immunity to develop, overproduction of the cytokine triggers immunopathological reactions. TS