Resistance to fever induction and impaired acute-phase response in interleukin-1β-deficient mice

Abstract We used gene targeting in embryonic stem cells to introduce an IL-1β null allele in mice. The IL-1β-deficient mice develop normally and are apparently healthy and fertile. The IL-1β null mice responded normally in models of contact and delayed-type hypersensitivity or following bacterial endotoxin LPS-induced inflammation. The IL-1β-deficlent mice showed equivalent resistance to Listeria monocytogenes compared with wild-type controls. In contrast, when challenged with turpentine, which causes localized inflammation and tissue injury, the IL-1β mutant mice exhibited an impaired acute-phase inflammatory response and were completely resistant to fever development and anorexia. These results highlight a central role for IL-1β as a pyrogen and a mediator of the acute-phase response in a subset of Inflammatory disease models, and support the notion that blocking the action of a single key cytokine can alter the course of specific immune and inflammatory responses.