Caspase‐1 is not involved in experimental hepatitis in mouse

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Abstract
Experimental hepatitis induced by tumor necrosis factor in d‐(+)‐galactosamine‐sensitized mice or by an agonistic anti‐Fas antibody in normal mice is accompanied by dramatic apoptosis of hepatocytes. Apoptosis is the final result of activation of a cascade of caspases. We used caspase‐1−/− mice, generated by gene targeting, to study the role of this protease in TNF‐ and anti‐Fas‐induced lethal hepatitis. We found that mutant mice exhibited the typical caspase‐1−/− phenotype, since they resisted to a lethal injection of LPS and released no interleukin‐1β in the circulation, in contrast to wild‐type littermates. When caspase‐1−/− mice were challenged with different doses of tumor necrosis factor/d‐(+)‐galactosamine or with anti‐Fas, no increased survival was observed compared with control mice. Furthermore, apoptosis in the livers of these mice and serum levels of alanine aminotransferase were not reduced. These data indicate that caspase‐1 deficiency does not lead to reduced apoptosis in these models, either because caspase‐1 is irrelevant in this model or because of functional redundancy.