Much interest has been focused on the proinflammatory cytokines, such as TNF♂, IL-1♂, IL-1♀, and IL-18, because these cytokines have critical roles in the immune and inflammatory reactions. Of these cytokines, IL-1 and IL-18 have common structural features, and indeed, their receptors form a family. They also share parts of a common signal transducing system, comprising IL-1 receptor-associated kinase (IRAK), MyD88, and TNF receptor-associated factor (TRAF-6), and activation of the transcription factor NF¶B. Although IL-1R type I and IL-18R♂ (IL-1Rrp) have a high homology, the receptors for each cytokine are expressed on different types of cells. For example, expression of IL-18R♂ (IL-18R), but not IL-1R type I, on T cells is upregulated by IL-12, a powerful differentiation factor for TH1. IL-18R♂ is now accepted as one of the surface markers for TH1 cells. IL-18, like IL-1, is expressed in a variety of tissues other than immune organs, and the expression of IL-18R in these tissues needs to be examined in relationship to its pathophysiological roles.