Hyperbilirubinemia exaggerates endotoxin-induced hypothermia

Cell Cycle
Eszter PakaiAndrej A Romanovsky

Abstract

Systemic inflammation is accompanied by an increased production of reactive oxygen species (ROS) and by either fever or hypothermia (or both). To study aseptic systemic inflammation, it is often induced in rats by the intravenous administration of bacterial lipopolysaccharide (LPS). Knowing that bilirubin is a potent ROS scavenger, we compared responses to LPS between normobilirubinemic Gunn rats (heterozygous, asymptomatic; J/+) and hyperbilirubinemic Gunn rats (homozygous, jaundiced; J/J) to establish whether ROS mediate fever and hypothermia in aseptic systemic inflammation. These two genotypes correspond to undisturbed versus drastically suppressed (by bilirubin) tissue accumulation of ROS, respectively. A low dose of LPS (10 μg/kg) caused a typical triphasic fever in both genotypes, without any intergenotype differences. A high dose of LPS (1,000 μg/kg) caused a complex response consisting of early hypothermia followed by late fever. The hypothermic response was markedly exaggerated, whereas the subsequent fever response was strongly attenuated in J/J rats, as compared to J/+ rats. J/J rats also tended to respond to 1,000 μg/kg with blunted surges in plasma levels of all hepatic enzymes studied (alanine aminotransferase, a...Continue Reading

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Citations

Aug 5, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Elizabeth A FlatowAlexandre A Steiner

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