Regulation of IL-18 expression in virus infection

Since its discovery as an interferon (IFN)-gamma -inducing factor, it has become evident that interleukin (IL)-18 plays a crucial role in the generation of protective immunity against microbial infections. Macrophages are the major source of biologically active IL-18, and they express constitutively IL-18 mRNA and proIL-18 protein. Microbial infections enhance the IL-18 gene expression in macrophages but post-translational processing of proIL-18, rather than transcriptional activation, is predominant in the regulation of IL-18 secretion. This review summarizes the current knowledge of proinflammatory and immunomodulatory properties of IL-18, and focuses on the role of caspases in the proteolytic activation of IL-18 in response to virus infection.