IFN-gamma-independent effects of IL-12 during intestinal nematode infection.

Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with a pronounced mastocytosis mediated by a Th2-type response involving IL-4, IL-10, and IL-13. When exogenous rIL-12 was administered to T. spiralis-infected NIH mice, this resulted in significant suppression of intestinal mast cell responses, delayed worm expulsion, increased muscle larvae burdens, and a transient, but significant decrease in early Th2 cytokine secretion. rIL-12 treatment also altered chemokine expression in the jejunal mucosa. The effects of exogenous IL-12 administration were largely independent of IFN-gamma as shown by rIL-12 treatment of IFN-gamma knockout mice. Hence, IL-12 may play a significant biological role as a direct negative regulator of intestinal Th2 responses and may act to promote the survival of intestinal parasites in vivo also in the absence of IFN-gamma.