DEFECTIVE NK CELL-ACTIVITY AND TH1 RESPONSE IN IL-18-DEFICIENT MICE

IL-18 is a cytokine that is secreted from activated macrophages and in duces IFN gamma production. To investigate the in vivo role of IL-18, we generated IL-18-deficient mice. In Propionibacterium acnes (P. acne s)-primed IL-18-deficient mice, LPS-induced IFN gamma production was m arkedly reduced, despite normal IL-12 induction. Natural killer cell a ctivity was significantly impaired. Th1 cell response after injection of P. acnes or Mycobacterium bovis (bacillus Calmette-Guerin [BCG]) wa s significantly reduced. Similar results were observed in IL-12-defici ent mice. Interestingly, Th1 response was induced after BCG infection in IL-12-deficient mice. We therefore generated mice lacking both IL-1 8 and IL-12. In these mice, NK activity and Th1 response were further impaired. This demonstrates the important role of both IL-18 and IL-12 in NK activity, as well as in in vivo Th1 response.