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

• Published in: The Journal of immunology (1950) Vol. 159; no. 5; pp. 2452 - 2461
• Main Authors: Labow, M, Shuster, D, Zetterstrom, M, Nunes, P, Terry, R, Cullinan, EB, Bartfai, T, Solorzano, C, Moldawer, LL, Chizzonite, R, McIntyre, KW
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.09.1997
• Subjects: Acute-Phase Reaction - physiopathology; Animals; Cells, Cultured; Disease Susceptibility; E-Selectin - biosynthesis; E-Selectin - genetics; Female; Fever - chemically induced; Fibroblasts - drug effects; Gene Targeting; Hypersensitivity, Delayed - physiopathology; Inflammation - physiopathology; Interleukin-1 - pharmacology; Interleukin-1 - toxicity; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Listeriosis - immunology; Male; Mice; Mice, Knockout; Receptors, Interleukin-1 - deficiency; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - physiology; Receptors, Interleukin-1 Type I; Signal Transduction; Turpentine - toxicity
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.159.5.2452

IL-1alpha and IL-1beta 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-1beta-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-1alpha and IL-1beta 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.