Mice deficient in IL-1 beta manifest impaired contact hypersensitivity to trinitrochlorobenzene

Mice rendered deficient in IL-1 beta by gene targeting in embryonic stem cells develop and grow normally in a protected laboratory environment. Endotoxin-stimulated peritoneal macrophages from IL-1 beta-deficient mice showed normal synthesis and cellular release of IL-1 alpha after treatment with 5 mM ATP demonstrating that IL-1 beta is not necessary for expression and release of the IL-1 alpha isoform. Mice deficient in IL-1 beta showed unaltered sensitivity to endotoxic shock, with or without pretreatment with D-galactosamine. In contrast, IL-1 beta-deficient mice showed defective contact hypersensitivity responses to topically applied trinitrochlorobenzene (TNCB). This defect could be overcome either by application of very high doses of sensitizing antigen, or by local intradermal injection of recombinant IL-1 beta immediately before antigen application. These data demonstrate an essential role for IL-1 beta in contact hypersensitivity and suggest that IL-1 beta acts early during the sensitization phase of the response. They suggest an important role for IL-1 beta in initiation of the host response at the epidermal barrier.