Icilin, a cool/cold-inducing agent, alleviates lipopolysaccharide-induced septic sickness responses in mice.

Abstract

Sepsis is a significant global public health challenge, resulting in millions of human deaths annually. Transient receptor potential melastatin 8 (TRPM8), a non-selective ion channel, is the primary cold sensor in humans; however, its effects on endotoxin-induced inflammation remain unclear. We previously reported that TRPM8 knockout mice exhibited more severe physiological and behavioral endotoxemia responses upon a high-dose injection with lipopolysaccharide (LPS). In the present study, we investigated whether icilin, a TRPM8 agonist, was a target for the suppression of sickness responses using a mouse model of LPS-induced sepsis. A peripheral high-dose injection of LPS at 5 mg/kg showed a maximal body temperature decrease of 5.1 °C in mice subcutaneously pretreated with vehicle and 1.5 °C in icilin-pretreated animals. The decline in locomotor activity was attenuated in icilin-pretreated mice and its recovery was faster; however, the high-dose LPS injection rapidly decreased locomotor activity regardless of the icilin pretreatment. Furthermore, the icilin pretreatment attenuated LPS-induced decreases in body weight and food and water intakes and accelerated recovery from these sickness responses. Therefore, the present results demonstrated that the icilin pretreatment alleviated LPS-induced sickness responses or decreases in body temperature, locomotor activity, body weight loss, and food and water intakes, suggesting its potential as a therapeutic target for sepsis.

• Authors: Mari Komura, Seiji Miyata, Ryoichi Yoshimura
• Journal: Neuroscience letters (Neurosci Lett) Vol. 816 Pg. 137492 (11 01 2023) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 37742941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Lipopolysaccharides
• icilin
• TRPM Cation Channels
• Water

Topics

• Humans
• Animals
• Mice
• Lipopolysaccharides
• TRPM Cation Channels (agonists)
• Sepsis (chemically induced, drug therapy)
• Water
• Cold Temperature