MICE DEFICIENT IN IL-1-BETA MANIFEST IMPAIRED CONTACT HYPERSENSITIVITY TO TRINITROCHLOROBENZENE

Mice rendered deficient in IL-1 beta by gene targeting in embryonic st em cells develop and grow normally in a protected laboratory environme nt. Endotoxin-stimulated peritoneal macrophages from IL-1 beta-deficie nt mice showed normal synthesis and cellular release of IL-1 alpha aft er treatment with 5 mM ATP demonstrating that IL-1 beta is not necessa ry for expression and release of the IL-1 alpha isoform. Mice deficien t in IL-1 beta showed unaltered sensitivity to endotoxic shock, with o r without pretreatment with D-galactosamine. In contrast, IL-1 beta-de ficient mice showed defective contact hypersensitivity responses to to pically applied trinitrochlorobenzene (TNCB). This defect could be ove rcome either by application of very high doses of sensitizing antigen, or by local intradermal injection of recombinant IL-1 beta immediatel y 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 sugges t an important role for IL-1 beta in initiation of the host response a t the epidermal barrier.