Hyperbilirubinemia exaggerates endotoxin-induced XXXX .

@entity32 @entity5428 @entity36392 @entity26 @entity648 @entity5906 @entity3929 @entity35 @entity99 @entity221 @entity2332
Systemic @entity32 is accompanied by an increased production of reactive @entity26 species (ROS) and by either @entity221 or @entity2332 (or both). To study @entity32 , it is often induced in @entity35 by the intravenous administration of bacterial lipopolysaccharide (LPS). Knowing that @entity648 is a potent ROS scavenger, we compared responses to LPS between normobilirubinemic @entity35 (heterozygous, asymptomatic; J/+) and @entity36392 @entity35 (homozygous, jaundiced; J/J) to establish whether ROS mediate @entity221 and @entity2332 in @entity32 . These two genotypes correspond to undisturbed versus drastically suppressed (by @entity648 ) tissue accumulation of ROS, respectively. A low dose of LPS (10  g/kg) caused a typical triphasic @entity221 in both genotypes, without any intergenotype differences. A high dose of LPS (1,000  g/kg) caused a complex response consisting of early @entity2332 followed by late @entity221 . The hypothermic response was markedly exaggerated, whereas the subsequent @entity221 response was strongly attenuated in J/J @entity35 , as compared to J/+ @entity35 . J/J @entity35 also tended to respond to 1,000  g/kg with blunted surges in plasma levels of all hepatic enzymes studied ( @entity3929 aminotransferase, @entity5906 aminotransferase, @entity5428 transferase), thus suggesting an attenuation of @entity99 . We propose that the reported exaggeration of LPS-induced @entity2332 in J/J @entity35 occurs via direct inhibition of nonshivering thermogenesis by @entity648 and possibly via a direct vasodilatatory action of @entity648 in the skin. This @entity2332 -exaggerating effect might be responsible, at least in part, for the observed tendency of J/J @entity35 to be protected from LPS-induced @entity99 . The attenuation of the @entity221 response to 1,000  g/kg could be due to either direct actions of @entity648 on thermoeffectors or the ROS-scavenging action of @entity648 . However, the experiments with 10  g/kg strongly suggest that ROS signaling is not involved in the @entity221 response to low doses of LPS.
