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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Apoptosis, B-Lymphocytes, Caspase 1, Disease Models, Animal, Escherichia coli Infections, Interleukin-18, Interleukin-1beta, Macrophages, Mice, Mice, Knockout, Phenotype, Sepsis, Spleen.
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Does caspase-1 regulate Escherichia coli sepsis and splenic B cell apoptosis independently of interleukin-1beta and interleukin-18? Context: Caspase-1 processes interleukin 1beta (IL-1beta) and IL-18 but may also contribute to apoptosis. In this context, caspase-1 knockout mice have been shown to be protected from endotoxin-induced mortality, whereas IL-1beta knockout mice are not protected. We therefore sought to delineate the mechanisms responsible for the differential responses between caspase-1 and IL-1beta knockout mice. Caspase-1 knockout, IL-1beta knockout, and IL-1beta/IL-18 double knockout mice were compared with wild-type mice for survival after intraperitoneal challenge with live Escherichia coli. Caspase-1 knockout animals were protected from bacterial challenge, whereas wild-type, IL-1beta knockout, and IL-1beta/IL-18 double knockout animals were not. Wild-type animals and both IL-1beta knockout and IL-1beta/IL-18 double knockout mice demonstrated significant splenic B lymphocyte apoptosis, which was absent in the caspase-1 knockout mice. Importantly, IL-1beta/IL-18 double knockout mice were protected from splenic cell apoptosis and sepsis-induced mortality by the caspase inhibitor zVAD-fmk. Furthermore, wild-type but not caspase-1 knockout splenic B lymphocytes induced peritoneal macrophages to assume an inhibitory phenotype.
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Taken together, these findings suggest that caspase-1 is important in the host response to sepsis at least in part via its ability to regulate sepsis-induced splenic cell apoptosis. Final Decision: yes