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Hepatic cytokine response can be modulated using the Kupffer cell blocker gadolinium chloride in obstructive jaundice.

AbstractINTRODUCTION:
Depletion of Kupffer cells by gadolinium chloride (GdCl(3)) reduces the systemic response during sepsis. The study aim was to investigate the effect of this depletion on hepatic proinflammatory cytokine response to portal endotoxaemia.
METHODS:
Sixteen Wistar rats were randomised to receive either saline IV (n = 8) or GdCl(3) (10 mg/kg IV, n = 8) six days after bile duct ligation (BDL). 24 h later the animals were perfused for 2 h, using isolated hepatic perfusion. Aliquots of effluent perfusate were collected at 20-min intervals for cytokine analysis. Sections of liver were sampled and the hepatic Kupffer cell number of each group was measured using ED1 immunohistochemistry.
RESULTS:
Pre-treatment with GdCl(3) resulted in significantly reduced serum bilirubin concentrations but significantly elevated serum ALP and AST levels compared to the control group. It was also associated with a significant reduction in Kupffer cell numbers and a corresponding significant reduction in hepatic TNFα and IL-6 production in response to portal endotoxaemia.
CONCLUSIONS:
Pre-treatment with GdCl(3) in jaundiced animals reduced Kupffer cell numbers, attenuated liver enzyme abnormalities and reduced TNFα and IL-6 in response to portal endotoxaemia. Hepatic Kupffer cells, therefore, play a significant role in the development of an exaggerated inflammatory response in obstructive jaundice.
AuthorsC Jones, S A Badger, M Hoper, R W Parks, T Diamond, M A Taylor
JournalInternational journal of surgery (London, England) (Int J Surg) Vol. 11 Issue 1 Pg. 46-51 ( 2013) ISSN: 1743-9159 [Electronic] England
PMID23168237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Gadolinium
  • gadolinium chloride
  • Bilirubin
Topics
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Bilirubin (blood)
  • Body Weight (drug effects)
  • Cell Count
  • Endotoxemia (blood, metabolism, pathology)
  • Gadolinium (pharmacology)
  • Immunohistochemistry
  • Interleukin-6 (metabolism)
  • Jaundice, Obstructive (blood, metabolism, pathology)
  • Kupffer Cells (drug effects, metabolism, pathology)
  • Liver (chemistry, drug effects, enzymology, metabolism)
  • Male
  • Mice
  • Perfusion
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha (metabolism)

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