Enhanced Hyperthermic Responses to Lipopolysaccharide in Mice Exposed to Repeated Cold Stress

Pharmacology. 2017;99(3-4):172-178. doi: 10.1159/000454815. Epub 2017 Jan 4.


Lipopolysaccharide (LPS) induces hyperthermia accompanied by various other systemic inflammatory symptoms. The rodents exposed to repeated cold (RC) stress according to a specific schedule are useful as experimental models for autonomic imbalance or fibromyalgia. It is now proven that RC-stressed mice exhibit tolerance to LPS, we examined thermal responses to LPS challenge in RC-stressed mice by monitoring core temperature using the telemetry system. Systemic administration of LPS caused bimodal hyperthermic responses in RC-stressed and unstressed mice. The magnitude of the LPS-induced hyperthermia was greater in RC-stressed mice than in unstressed mice. The RC stress-induced enhancement of hyperthermic responses to LPS was abolished by pretreatment with diclofenac, which is a cyclooxygenase (COX) inhibitor. LPS did not significantly increase COX-2 protein levels in the lung or hypothalamus of RC-stressed or unstressed mice. RC stress did not alter baseline serum corticosterone levels or their increases in response to LPS challenge. These results suggest that RC stress enhances the susceptibility of mice to LPS challenge, leading to greater prostanoid-dependent hyperthermia, which might contribute to tolerance to LPS in RC-stressed mice.

MeSH terms

  • Animals
  • Body Temperature / physiology
  • Circadian Rhythm / physiology*
  • Cold Temperature / adverse effects*
  • Corticosterone / blood
  • Cyclooxygenase 2 / biosynthesis
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology*


  • Lipopolysaccharides
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Corticosterone