Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice.
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.
Labow
M
M
Hoffmann-La Roche, Nutley, NJ 07110, USA. Mark.Labow@roche.com
Shuster
D
D
Zetterstrom
M
M
Nunes
P
P
Terry
R
R
Cullinan
E B
EB
Bartfai
T
T
Solorzano
C
C
Moldawer
L L
LL
Chizzonite
R
R
McIntyre
K W
KW
D000210:Acute-Phase Reaction / Q000503:physiopathology; D000818:Animals; D002478:Cells, Cultured; D004198:Disease Susceptibility; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005334:Fever / Q000139:chemically induced; D005347:Fibroblasts / Q000187:drug effects; D018390:Gene Targeting; D006968:Hypersensitivity, Delayed / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D007375:Interleukin-1 / Q000494:pharmacology* / Q000633:toxicity; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008088:Listeriosis / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D053573:Receptors, Interleukin-1 Type I; D015398:Signal Transduction; D014425:Turpentine / Q000633:toxicity
D019040:E-Selectin; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D014425:Turpentine