IL-12 MODULATION OF T-HELPER RESPONSES TO THE FILARIAL HELMINTH, BRUGIA-MALAYI

The purpose of the current study was to evaluate the effects of exogen ous IL-12 on: 1) development of the Th cell response to Brugia malayi microfilariae (mf); 2) established B. malayi-specific Th2 responses; a nd 3) resistance to mf. IL-12 given at the time of inoculation with li ve mf resulted in a switch in development from a dominant Th2 (IL-4, I L-5 >> IFN-gamma) to a dominant Th1 response (IFN-gamma >> IL-4, IL-5) . Induction of Th1 activity by IL-12 was dependent on IFN-gamma in viv o. When mice were given IL-12 (0.5 mu g daily for 4 days) after mf Ag- specific Th2 responses had been established, Ag-driven IL-4 and IL-5 p roduction by spleen and peritoneal cells were reduced respectively by similar to 75 to 90% and similar to 30 to 40%, IFN-gamma production wa s elevated, and 68% fewer eosinophils were recovered from the peritone al cavity. In vivo depletion of IFN-gamma ablated the effects of IL-12 on both cytokine production and eosinophil recovery. IL-12 treatment of either naive or previously sensitized mice challenged intravenously with live B. malayi did not alter the rate of clearance of mf from th e blood. These data indicate that IL-12 treatment suppresses induction of filarial driven Th2 responses and modulates recall responses of es tablished Th2 cells, but does not alter elimination of blood-borne mf in nonimmune or immune mice.