RESPONSE TO LOCAL INFLAMMATION OF IL-1-BETA-CONVERTING ENZYME-DEFICIENT MICE

IL-1 beta-converting enzyme (ICE) cleaves pro-IL-1 beta to the mature, released form. Although other proteases can process pro-IL-1 beta ICE -deficient (ICE -/-) mice do not release mature IL-1 beta in response to endotoxin. The purpose of our study was to investigate the response of ICE -/- mice in two models of local inflammation, turpentine-induc ed tissue damage and zymosan-induced peritonitis. No differences were observed in the development of the systemic acute phase response after turpentine administration between wild-type and ICE -/- mice, but thi s response was completely impaired in IL-1 beta -/- mice. Accordingly, the levels of mature IL-1 beta produced in response to turpentine did not differ between wild-type and ICE -/- mice. In contrast, following zymosan-induced peritonitis, the levels of mature IL-1 beta were sign ificantly lower in ICE -/- mice. This was associated with a 50% decrea se in cellular infiltrate in ICE -/- mice compared with that in wild-t ype controls. The reduced production of zymosan-induced mature IL-1 be ta in ICE -/- mice was also observed from cultured peritoneal or splee n cells. Our results demonstrate that in turpentine-induced tissue nec rosis, precursor IL-1 beta is processed by non-ICE proteases, but in c omplement-mediated inflammation, ICE participates in the processing of the IL-1 beta precursor.