Effect of interleukin-18 on mouse core body temperature

Abstract

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.

The Inflammasome Sensor, NLRP3, Regulates CNS Inflammation and Demyelination via Caspase-1 and Interleukin-18

“…Such a possibility is not without precedence. For example, another study has found that IL-18 negated the febrile effect associated with IL-1␤ (Gatti et al, 2002). In summary, the role of IL-18 in exacerbating neuroinflammation along with its inhibitory role in remyelination indicate that inhibition of IL-18 may prove to be a valuable therapeutic approach for demyelinating diseases such as MS.…”

Differences in signaling pathways by IL-1β and IL-18

“…Discussion IL-1␤, IL-18, COX-2, and Fever. The present study was performed to examine the differences between IL-1␤ and IL-18 for the induction of COX-2, because injection of IL-18 does not cause fever in animals (5,17,18). These data are in sharp contrast to the ability of IL-1 to produce fever in animals and humans at exceedingly low doses of a few nanograms per kilogram (13).…”

“…Although IL-18 has been reported to induce COX-2 gene expression in the articular chondrocytes (16), IL-18 does not cause fever (5,17,18), which depends on COX-2 (3,4). Humans, who are highly responsive to the rapid pyrogenic response of i.v.…”

The Inflammatory Caspases: Key Players in the Host Response to Pathogenic Invasion and Sepsis

“…Although they share certain proinflammatory activities, they also have very important individual functions. For example, IL-1␤ but not IL-18 is anorectic (40,41), pyrogenic (42,43), results in skin rashes and urticaria, induces hepatic-acute phase proteins (44,45), up-regulates prostanoid synthesis, and is involved in inflammatory pain hypersensitivity (46). IL-1␤ is also implicated in destructive joint and bone disease (47), tumor angiogenesis and invasiveness (48), and toxicity of insulin-producing pancreatic islets ␤ cells (49), and neurons in stroke and neurodegeneration (50).…”