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-1β, lipopolysaccharide (LPS), and recombinant murine interferon-γ (rmIFN-γ). Both IL-1β and LPS induced a febrile response within the first hour after the intraperitoneal injection, whereas rmIL-18 (10–200 μg/kg) and rmIFN-γ (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-1β, significantly reduced the IL-1β-induced fever response. In contrast, the same pretreatment with IL-18 did not modify the febrile response induced by LPS. IFN-γ does not seem to play a role in the IL-18-mediated attenuation of IL-1β-induced fever. In fact, there was no elevation of IFN-γ in the serum of mice treated with IL-18, and a pretreatment with IFN-γ did not modify the fever response induced by IL-1β. 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-1β, attenuates the febrile response induced by IL-1β.