title: Resistance to fever induction and impaired acute-phase response in interleukin-1 beta-deficient mice.
abstract: We used gene targeting in embryonic stem cells to introduce an IL-1 beta null allele in mice. The IL-1 beta-deficient mice develop normally and are apparently healthy and fertile. The IL-1 beta null mice responded normally in models of contact and delayed-type hypersensitivity or following bacterial endotoxin LPS-induced inflammation. The IL-1 beta-deficient 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-1 beta 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-1 beta 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.
authors.affiliation: Department of Genetics and Molecular Biology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.forename: D
authors.initials: D
authors.lastname: Fletcher
authors.forename: W
authors.initials: W
authors.lastname: Kozak
authors.forename: M
authors.initials: M
authors.lastname: Jiang
authors.forename: K J
authors.initials: KJ
authors.lastname: Hofmann
authors.forename: C A
authors.initials: CA
authors.lastname: Conn
authors.forename: D
authors.initials: D
authors.lastname: Soszynski
authors.forename: C
authors.initials: C
authors.lastname: Grabiec
authors.forename: M E
authors.initials: ME
authors.lastname: Trumbauer
authors.forename: A
authors.initials: A
authors.lastname: Shaw
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005334:Fever / Q000378:metabolism* / Q000517:prevention & control; D007375:Interleukin-1 / Q000172:deficiency*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides