Interleukin-1 signal transduction

Interleukin 1 (IL1) is a potent pro-inflammatory cytokine which has been implicated in the pathogenesis of chronic inflammatory disease. Despite much effect, the signal transduction pathway activated by IL1 has remained obscure. Recently, much attention has focussed on IL1 receptors and early events triggered by IL1 in cells, including activation of transcription factors and serine/threonine protein kinases. Two main types of IL1 receptors have been described, IL1RI and IL1RII. They appear to belong to a family of proteins which include most notably a Drosophila protein, Toll. Following receptor binding IL1 has been shown to increase protein phosphorylation in cells, and much effort has been made to identify the protein kinases responsible. Novel enzymes have been discovered, including a family of MAP kinase--like enzymes which are also activated by a range of stresses such as hypertonic stress and heat shock. Attention has also been focussed in the activation of the transcription factor NF kappa B, which is rapidly activated by IL1. This review will describe our current understanding of how IL1 activated cells and will particularly describe more recent work on IL1 receptors and early post-receptors events.