Hyperbilirubinemia exaggerates endotoxin-induced hypothermia

Area of Science:

• Physiology
• Immunology
• Biochemistry

Background:

• Systemic inflammation involves increased reactive oxygen species (ROS) and altered body temperature (fever/hypothermia).
• Bacterial lipopolysaccharide (LPS) is commonly used to induce aseptic systemic inflammation in animal models.
• Bilirubin is a potent endogenous antioxidant and ROS scavenger.

Purpose of the Study:

• To investigate the role of ROS in mediating fever and hypothermia during LPS-induced systemic inflammation.
• To compare the inflammatory responses to LPS in rats with normal bilirubin levels (J/+) versus hyperbilirubinemic rats (J/J).

Main Methods:

• Intravenous administration of two different doses of LPS (10 μg/kg and 1,000 μg/kg) to normobilirubinemic (J/+) and hyperbilirubinemic (J/J) Gunn rats.
• Monitoring of body temperature (fever and hypothermia) and plasma levels of hepatic enzymes (ALT, AST, GGT).
• Comparison of responses between the two genotypes to assess the effect of bilirubin on inflammation and ROS.

Main Results:

• Low-dose LPS (10 μg/kg) induced similar triphasic fever in both genotypes, indicating ROS are not involved in low-dose fever.
• High-dose LPS (1,000 μg/kg) caused exaggerated hypothermia and attenuated fever in hyperbilirubinemic J/J rats compared to J/+ rats.
• J/J rats showed reduced hepatic damage, evidenced by lower plasma hepatic enzyme levels, suggesting protection from LPS-induced injury.

Conclusions:

• Bilirubin's exaggerated hypothermia effect in J/J rats may be due to direct inhibition of thermogenesis and vasodilation.
• The protective effect against LPS-induced hepatic damage in J/J rats might be linked to the hypothermia-exaggerating effect of bilirubin.
• ROS signaling is not implicated in the fever response to low-dose LPS, but bilirubin's ROS-scavenging action may contribute to fever attenuation at high LPS doses.