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Tumor necrosis factor-alpha and interleukin-6 reduce bile canalicular contractions of rat hepatocytes.

Authors: Ikeda, Shinichiro  Mitaka, Toshihiro  Harada, Keisuke  Sato, Fumihiko  Mochizuki, Yohichi  Hirata, Koichi 
Citation: Ikeda S, etal., Surgery. 2003 Jan;133(1):101-9. doi: 10.1067/msy.2003.91.
Pubmed: (View Article at PubMed) PMID:12563244
DOI: Full-text: DOI:10.1067/msy.2003.91

BACKGROUND: Surgeons sometimes encounter hyperbilirubinemia without mechanical obstruction of the biliary tree postoperatively. Many of these patients have bacterial infections and endotoxemia. Kupffer's cells stimulated by endotoxin secrete inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. We hypothesized that TNF-alpha and IL-6 might be involved in the pathogenesis of hyperbilirubinemia.
METHODS: Effects of TNF-alpha and IL-6 on the contractions of bile canaliculi (BC) of rat hepatocyte couplets were examined and time-lapse images using phase-contrast microscopy were taken. Bile was collected from rats treated with or without the cytokines. The livers, perfused with lanthanum after the injection of cytokines, were examined ultrastructurally using electron microscopy.
RESULTS: The number of BC contractions decreased in the couplets treated with both cytokines. The rapid movement of a droplet from BC was observed at the intercellular space of the hepatocyte couplet treated with TNF-alpha. Systolic blood pressure and hepatic tissue blood flow of rats injected with TNF-alpha were not changed, whereas the hepatic tissue blood flow of rats treated with IL-6 decreased (Dunnett test, P <.05). Bile secretion was reduced in both groups of rats (Dunnett test, P <.05). In rats treated with TNF-alpha the total serum bile acid concentration increased and lanthanum temporarily accumulated in BC.
CONCLUSIONS: These results suggest that TNF-alpha and IL-6 may reduce BC contractions and thereby decrease bile flow.


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RGD Object Information
RGD ID: 14995483
Created: 2019-10-28
Species: All species
Last Modified: 2019-10-28
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.