ICE family proteases in inflammation and apoptosis

The interleukin-1 beta converting enzyme (ICE) was first identified as a unique cysteine protease that processes the inactive precursor of the pro-inflammatory cytokine IL-1 beta to its mature active form. Subsequent revelation that a C. elegans cell death gene ced-3 bears sequence homology to ICE has led to rapid identification of at least nine other members of this gene family in humans, some of which are involved in apoptosis. Analyses of ICE-deficient mice generated by gene targeting technology reveal that this enzyme is important in maturation of several cytokines. The ICE deficient mice are resistant in several models of localized and systemic inflammation. ICE itself, however, is not required for Fas-mediated apoptosis, a physiological process for elimination of activated lymphocytes. Selective inhibitors of ICE would be novel therapeutic agents for treatment of diseases where excess inflammation contributes to pathological processes.