Interleukin-1.

Interleukin-1 (IL-1) is the prototypic pro-inflammatory cytokine. There are two forms of IL-1, IL-1alpha and IL-1beta and in most studies, their biological activities are indistinguishable. IL-1 affects nearly every cell type, often in concert with another pro-inflammatory cytokine, tumor necrosis factor (TNF). Although IL-1 can upregulate host defenses and function as an immunoadjuvant, IL-1 is a highly inflammatory cytokine. The margin between clinical benefit and unacceptable toxicity in humans is exceedingly narrow. In contrast, agents that reduce the production and/or activity of IL-1 are likely to have an impact on clinical medicine. The synthesis, processing, secretion and activity of IL-1, particularly IL-1beta, are tightly regulated events. A unique aspect of cytokine biology is the naturally occurring IL-1 receptor antagonist (IL-1Ra). IL-1Ra is structurally similar to IL-1beta but lacking agonist activity is used in clinical trials to reduce disease severity. In addition, regulation of IL-1 activity extends to low numbers of surface receptors, circulating soluble receptors and a cell surface "decoy" receptor to down-regulate responses to IL-1beta. This review updates the current knowledge on IL-1.