title: Hepatic cytokine response can be modulated using the Kupffer cell blocker gadolinium chloride in obstructive jaundice.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Queens University Belfast, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Jones
authors.forename: S A
authors.initials: SA
authors.lastname: Badger
authors.forename: M
authors.initials: M
authors.lastname: Hoper
authors.forename: R W
authors.initials: RW
authors.lastname: Parks
authors.forename: T
authors.initials: T
authors.lastname: Diamond
authors.forename: M A
authors.initials: MA
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001663:Bilirubin / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D019446:Endotoxemia / Q000097:blood / Q000378:metabolism / Q000473:pathology; D005682:Gadolinium / Q000494:pharmacology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism*; D041781:Jaundice, Obstructive / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D010477:Perfusion; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005682:Gadolinium; C038958:gadolinium chloride; D001663:Bilirubin