Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice

IL-1 alpha and IL-1 beta are potent inflammatory cytokines that contribute to a number of normal physiologic processes and to the development of a number of inflammatory diseases, Two IL-1R, the type I and type II receptors, have been identified, This work describes the derivation and characterization of mice deficient in expression of the type I IL-1R (IL-1RI), IL-1RI-deficient mice were viable and fertile, but failed to respond to IL-1 in a variety of assays, including IL-1-induced IL-6 and E-selectin expression and IL-1-induced fever, Similar to IL-1 beta-deficient mice, IL-1RI-deficient mice had a reduced acute phase response to turpentine, In contrast, IL-1RI-deficient mice had a reduced delayed-type hypersensitivity response and were highly susceptible to infection by Listeria monocytogenes, These data demonstrate that the IL-1RI is essential for all IL-1-mediated signaling events examined, and that both IL-1 alpha and IL-1 beta are critical to the animals' response to injury and infection, These data also demonstrate that IL-1 function is not required for normal development or homeostasis.