| First Author | Sewnath ME | Year | 2002 |
| Journal | Hepatology | Volume | 35 |
| Issue | 1 | Pages | 149-58 |
| PubMed ID | 11786971 | Mgi Jnum | J:105837 |
| Mgi Id | MGI:3616746 | Doi | 10.1053/jhep.2002.30272 |
| Citation | Sewnath ME, et al. (2002) Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin. Hepatology 35(1):149-58 |
| abstractText | Cholestatic liver injury is associated with an increased susceptibility toward endotoxin-induced toxicity. To determine the role of interleukin 1 (IL-1) herein, extrahepatic cholestasis was induced by bile duct ligation (bdl) in IL-1 receptor type I gene-deficient (IL-1R(-/-)) mice, which are unresponsive to IL-1alpha and IL-1beta, and normal IL-1R(+/+) mice. Bdl elicited increases in hepatic IL-1alpha and IL-1beta messenger RNA (mRNA) and protein. Hepatocellular injury at 2 weeks after bdl was similar in IL-1R(-/-) and IL-1R(+/+) mice as shown by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice at 2 weeks after bdl was associated with enhanced cytokine release, more severe liver damage, and occurrence of death when compared with sham-operated mice. Endotoxin effects in sham-operated IL-1R(-/-) and IL-1R(+/+) mice were largely similar, but cholestatic IL-1R(-/-) mice were better protected against toxic effects of endotoxin, as reflected by lowered cytokine release, less profound liver injury, and reduced mortality. These data indicate that IL-1alpha and IL-1beta are produced in the liver after bdl, but that these cytokines do not play a significant role in cholestatic liver damage; however, endogenous IL-1 activity is an important denominator of enhanced endotoxin sensitivity that is observed during cholestasis induced by bdl. |
