Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand

Fas ligand is a well-characterized Apoptosis inducer. Here we demonstrate that Fas ligand induces the processing and secretion of interleukin-1beta (IL-1beta) in peritoneal exudate cells. This IL-1beta secretion is independent of IL-1beta converting Enzyme (Caspase 1), yet it is inhibited by Caspase inhibitors, indicating that a Caspase(s) in addition to IL-1beta converting Enzyme can process IL-1beta. Inoculation of tumor cells expressing Fas ligand into wild-type mice induces a massive neutrophil infiltration that is, in contrast, suppressed in IL-1alpha/beta knockout mice. These results demonstrate a newly discovered role for Fas ligand in inflammation, and challenge the dogma that Apoptosis does not induce inflammation.