Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu.

IL-18 is a potent proinflammatory cytokine able to induce IFNgamma, GM-CSF, TNFalpha and IL-1 in immunocompetent cells, to activate killing by lymphocytes, and to up-regulate the expression of certain chemokine receptors. IL-18 is also essential to host defences against severe infections. In particular, the clearance of intracellular bacteria, fungi and protozoa requires the induction of host-derived IFNgamma, which evokes effector molecules such as nitric oxide. Also, IL-18 plays a part in the clearance of viruses, partly by the induction of cytotoxic T cells, and the expulsion of viruses is impaired in IL-18-deficient mice. IL-18 also enhances tumour rejection by its potent capacity to augment the cytotoxic activity of NK and T cells in vivo. In contrast, recent studies also demonstrate a convincing role for IL-18 in atopic responses, including atopic asthma. IL-18 induces naive T cells to develop into Th2 cells. Moreover, IL-18 also induces IL-13 and/or IL-4 production by NK cells, mast cells and basophils. Therefore, IL-18 should be seen as a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses.