Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock

Abstract IL-1β-converting enzyme (ICE) cleaves pro-1L-1β to generate mature IL-1β. ICE is homologous to other proteins that have been implicated in apoptosis, including CED-3 and Nedd-2/Ich-1. We generated ICE -deficient mice and observed that they are overtly normal but have a major defect in the production of mature IL-1β after stimulation with lipopolysaccharide. IL-1α production is also impaired. ICE -deficient mice are resistant to endotoxic shock. Thymocytes and macrophages from the ICE -deficient animals undergo apoptosis normally. ICE therefore plays a dominant role in the generation of mature IL-1β, a previously unsuspected role in production of IL-1α, but has no autonomous function in apoptosis.