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

• Published in: The Journal of immunology (1950) Vol. 159; no. 7; pp. 3364 - 3371
• Main Authors: Glaccum, MB, Stocking, KL, Charrier, K, Smith, JL, Willis, CR, Maliszewski, C, Livingston, DJ, Peschon, JJ, Morrissey, PJ
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.10.1997
• Subjects: Acute-Phase Proteins - biosynthesis; Animals; Caspase 1; Cysteine Endopeptidases - deficiency; Cysteine Endopeptidases - genetics; Disease Susceptibility; Female; Immunity, Innate; Interleukin-1 - pharmacology; Interleukin-6 - biosynthesis; Interleukin-6 - blood; Lipopolysaccharides - toxicity; Listeriosis - immunology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout - genetics; Mice, Knockout - immunology; Phenotype; Receptors, Interleukin-1 - deficiency; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.159.7.3364

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 I IL-1R-/- double mutant mice are resistant to high dose LPS. Type I IL-1R-/- mice backcrossed to the C57BL/6 background were as equally resistant as wild-type mice to Listeria monocytogenes.