Phenotypic and functional characterization of mice that lack the type I receptor for IL-1

IL-1 alpha and IL-1 beta bind to receptors termed the type I and type II IL-1 receptors, The type I IL-1 receptor is responsible for specific signaling, while the type II IL-1 receptor functions as a nonsignaling decoy receptor. To determine the effect of a defect in IL-1-mediated signaling, mice have been produced with a genetically disrupted type I IL-1 receptor gene, Mice lacking type I IL-1 receptors are of normal vigor and exhibit no overt phenotype, B cells from type I IL-1R(-/-) mice activated in vitro with anti-IgM do not proliferate in response to IL-1, but do so in response to IL-4, Injection of murine IL-1 alpha does not induce detectable serum IL-6 levels in type I IL-1R(-/-) mice, but equivalent levels are produced in response to LPS. Type I IL-1R(-/-) mice have normal serum Ig levels and generate equivalent primary and secondary Ab responses as wild-type mice, In response to LPS, acute phase protein mRNA induction are equivalent in type I IL-1R(-/-) and wild-type mice, Type I IL-1R(-/-) mice do not differ from control mice in susceptibility to either a lethal challenge with D-galactosamine plus LPS or high dose LPS. Interestingly, ICE-/-/type 1 IL-1R(-/-) double mutant mice are resistant to high dose LPS. Type I IL-1R(-/-) mice backcrossed to the C578L/6 background were as equally resistant as wild-type mice to Listeria monocytogenes.