INTERLEUKIN-12 INDUCTION OF INTERFERON-GAMMA DEPENDENT PROTECTION AGAINST MALARIA

Intraperitoneal injection of recombinant Interleukin 12 (rIL-12) at 30 ng/day for 5 days beginning 1 to 2 days before sporozoite challenge o r administration of a single dose of 150 ng of rIL-12 2 days before ch allenge protected 100% of BALB/c mice against challenge with 10(2) Pla smodium yoelii sporozoites. rIL-12-induced protection was eliminated i n all mice by administration of a monoclonal antibody against interfer on gamma and in 50% of mice by administration of N-G-monomethyl-L-argi nine, a competitive inhibitor of nitric oxide synthase. rIL-12 protect ed BALB/c mice treated with cytotoxic anti-CD4 and anti-CD8 monoclonal antibodies, as well as T-cell- and B-cell-deficient severe combined i mmunodeficiency mice. These data suggest that rIL-12 stimulates non-B, non-T cells to produce interferon gamma that kills intrahepatic paras ites by stimulating nitric oxide production. If rIL-12 proves to be we ll tolerated by humans, our findings support consideration of rIL-12 a s an immunoprophylactic against malaria.