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 exogenous IL-12 on: 1) development of the Th cell response to Brugia malayi microfilariae (mf); 2) established B. malayi-specific Th2 responses; and 3) resistance to mf. IL-12 given at the time of inoculation with live mf resulted in a switch in development from a dominant Th2 (IL-4, IL-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 vivo. 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 production by spleen and peritoneal cells were reduced respectively by similar to 75 to 90% and similar to 30 to 40%, IFN-gamma production was elevated, and 68% fewer eosinophils were recovered from the peritoneal 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 the blood. These data indicate that IL-12 treatment suppresses induction of filarial driven Th2 responses and modulates recall responses of established Th2 cells, but does not alter elimination of blood-borne mf in nonimmune or immune mice.