Resistance to fever induction and impaired acute-phase response in interleukin-1 beta-deficient mice.
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.
Zheng
H
H
Department of Genetics and Molecular Biology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Fletcher
D
D
Kozak
W
W
Jiang
M
M
Hofmann
K J
KJ
Conn
C A
CA
Soszynski
D
D
Grabiec
C
C
Trumbauer
M E
ME
Shaw
A
A
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
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides