Abstract | BACKGROUND: Although hepatocellular dysfunction occurs early after the onset of sepsis, the mechanism responsible for this remains unknown. We tested the hypothesis that the reduction in Kupffer cell (KC) numbers prior to the onset of sepsis prevents the occurrence of hepatocellular dysfunction and reduces levels of the proinflammatory cytokines IL-1beta and IL-6 during the early stage of polymicrobial sepsis. MATERIALS AND METHODS: RESULTS: Hepatocellular function was depressed and the circulating levels of IL-1beta and IL-6 were increased significantly at 5 h after CLP. KC reduction by prior administration of gadolinium chloride, however, prevented the occurrence of hepatocellular dysfunction and the upregulation of IL-1beta and IL-6. CONCLUSIONS: The KC-derived proinflammatory cytokines IL-1beta and IL-6 appear to be directly or indirectly responsible for producing hepatocellular dysfunction during early sepsis. Thus, pharmacologic agents that downregulate the production of one or both of these proinflammatory cytokines in the liver may be useful for maintaining hepatocellular function during the early stage of sepsis.
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Authors | D J Koo, I H Chaudry, P Wang |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 83
Issue 2
Pg. 151-7
(May 15 1999)
ISSN: 0022-4804 [Print] United States |
PMID | 10329110
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Copyright 1999 Academic Press. |
Chemical References |
- Cytokines
- Interleukin-1
- Interleukin-6
- Gadolinium
- gadolinium chloride
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Topics |
- Animals
- Biological Transport
- Cecum
- Cytokines
(biosynthesis)
- Disease Models, Animal
- Gadolinium
(pharmacology)
- Inflammation
- Interleukin-1
(biosynthesis)
- Interleukin-6
(biosynthesis)
- Kupffer Cells
(immunology, metabolism, pathology)
- Male
- Rats
- Rats, Sprague-Dawley
- Reference Values
- Sepsis
(immunology, metabolism, pathology)
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