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 specifi c signaling, while the type II IL-1 receptor functions as a nonsignali ng decoy receptor. To determine the effect of a defect in IL-1-mediate d signaling, mice have been produced with a genetically disrupted type I IL-1 receptor gene, Mice lacking type I IL-1 receptors are of norma l 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(-/-) mic e, 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, acu te phase protein mRNA induction are equivalent in type I IL-1R(-/-) an d wild-type mice, Type I IL-1R(-/-) mice do not differ from control mi ce in susceptibility to either a lethal challenge with D-galactosamine plus LPS or high dose LPS. Interestingly, ICE-/-/type 1 IL-1R(-/-) do uble mutant mice are resistant to high dose LPS. Type I IL-1R(-/-) mic e backcrossed to the C578L/6 background were as equally resistant as w ild-type mice to Listeria monocytogenes.