Effect of interleukin-18 on mouse core body temperature.
We have studied, using a telemetry system, the pyrogenic properties of recombinant murine interleukin-18 (rmIL-18) injected into the peritoneum of C57BL/6 mice. The effect of IL-18 was compared with the febrile response induced by human IL-1beta, lipopolysaccharide (LPS), and recombinant murine interferon-gamma (rmIFN-gamma). Both IL-1beta and LPS induced a febrile response within the first hour after the intraperitoneal injection, whereas rmIL-18 (10-200 microg/kg) and rmIFN-gamma (10-150 microg/kg) did not cause significant changes in the core body temperature of mice. Surprisingly, increasing doses of IL-18, injected intraperitoneally 30 min before IL-1beta, significantly reduced the IL-1beta-induced fever response. In contrast, the same pretreatment with IL-18 did not modify the febrile response induced by LPS. IFN-gamma does not seem to play a role in the IL-18-mediated attenuation of IL-1beta-induced fever. In fact, there was no elevation of IFN-gamma in the serum of mice treated with IL-18, and a pretreatment with IFN-gamma did not modify the fever response induced by IL-1beta. We conclude that IL-18 is not pyrogenic when injected intraperitoneally in C57BL/6 mice. Furthermore, a pretreatment with IL-18, 30 min before IL-1beta, attenuates the febrile response induced by IL-1beta.
Gatti
Silvia
S
Pharmaceutical Division, CNS Preclinical Research, F. Hoffmann-LaRoche, CH-4070 Basel, Switzerland. silvia.gatti@roche.com
Beck
Jennifer
J
Fantuzzi
Giamila
G
Bartfai
Tamas
T
Dinarello
Charles A
CA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004357:Drug Synergism; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D006801:Humans; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology; D020382:Interleukin-18 / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D007375:Interleukin-1; D020382:Interleukin-18; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma