EFFECTS OF INTERLEUKIN-12 ON IMMUNE-RESPONSES AND HOST PROTECTION IN MICE INFECTED WITH INTESTINAL NEMATODE PARASITES

The cytokine interleukin (IL) 12 stimulates T cell and natural killer cell Production of interferon (IFN) gamma and inhibits T cell producti on of IL-4. We investigated the effects of IL-12 on cytokine gene expr ession, immunoglobulin (Ig)E, mucosal mast cell, and eosinophil respon ses, and the course of infection in mice inoculated with the nematode parasite Nippostrongylus brasiliensis, as well as the IFN-gamma depend ence of these effects. IL-12 stimulated IFN-gamma and IL-10 gene expre ssion during primary and secondary N. Brasiliensis infections and inhi bited IL-3; IL-4, IL-5, and IL-9 gene expression during primary infect ions but had little inhibitory effect during secondary infections. IL- 12 inhibited IgE, mucosal mast cell, and blood and tissue eosinophil r esponses during primary infections, but only eosinophil responses duri ng secondary infections. IL-12 enhanced adult worm survival and egg pr oduction during primary, but not secondary infections. IL-12 needed to be administered by day 4 of a primary infection to inhibit IgE and mu cosal mast cell responses, and by day 6 to strongly inhibit eosinophil responses and to enhance worm survival and fecundity. Anti-IFN-gamma mAb inhibited the effects of IL-12 on IgE secretion, intestinal mucosa l mastocytosis, and parasite survival and fecundity, but did not affec t IL-12 inhibition of eosinophilia. These observations indicate that I L-12, if administered during the initiation of an immune response, can change the response from one that is characterized by the production of T helper (Th)2-associated cytokines to one characterized by the pro duction of Th-l associated cytokines. However, IL-12 treatment has les s of an effect once the production of Th2-associated cytokines has bec ome established. In addition, our results provide evidence that Th2-as sociated responses protect against, and/or Th1-associated responses ex acerbate, nematode infections.