Mice rendered deficient in IL-1β by gene targeting in embryonic stem cells develop and grow normally in a protected laboratory environment. Endotoxin-stimulated peritoneal macrophages from IL-1β-deficient mice showed normal synthesis and cellular release of IL-1α after treatment with 5 mM ATP demonstrating that IL-1β is not necessary for expression and release of the IL-1α isoform. Mice deficient in IL-1β showed unaltered sensitivity to endotoxic shock, with or without pretreatment with D-galactosamine. In contrast, IL-1β-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-lβ immediately before antigen application. These data demonstrate an essential role for IL- 1β in contact hypersensitivity and suggest that IL-1β acts early during the sensitization phase of the response. They suggest an important role for IL- 1β in initiation of the host response at the epidermal barrier.
