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Am J Physiol Regul Integr Comp Physiol 282: R702-R709, 2002; doi:10.1152/ajpregu.00393.2001
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Vol. 282, Issue 3, R702-R709, March 2002

Effect of interleukin-18 on mouse core body temperature

Silvia Gatti1, Jennifer Beck1, Giamila Fantuzzi2, Tamas Bartfai1, and Charles A. Dinarello2

1 Pharmaceutical Division, CNS Preclinical Research, F. Hoffmann-LaRoche, CH-4070 Basel, Switzerland; and 2 Division of Infectious Diseases, University of Colorado Health Science Center, Denver, Colorado 80262

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 µg/kg) and rmIFN-gamma (10-150 µg/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 .

interleukin-1beta ; interferon-gamma


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