Glucocorticoid treatment down-regulates chemokine expression of bacterial cholangitis in cholestatic rats

J Pediatr Surg. 2004 Jan;39(1):10-5. doi: 10.1016/j.jpedsurg.2003.09.012.

Abstract

Background: Postoperative cholangitis is common after operation for biliary atresia. Empirical pulse therapy with glucocorticoid is effective in reversing some detrimental clinical manifestations, but the rationale for such a therapy still is not substantiated.

Methods: Adult male rats were divided into groups according to the treatment: sterile normal saline (NS) or Escherichia coli (EC, 1 mL containing 10(8) cells of ATCC 25922 strain), 1 mL, were infused into the proximal choledochostomy (PC) tube 2 weeks after ligation of the PC tube (bile duct ligation, BDL), then immediate tube-tube choledocho-choledochostomy (biliary drainage, BD) was constructed. A high dose of dexamethasone (DEX, intraperitoneal injection; 2 mg/kg of body weight) was given after BD in treatment groups. Histopathology of the liver, as well as liver chemokine mRNA expression and serum chemokine levels, were studied 24 hours after treatment.

Results: Inflammatory cell infiltration to the liver was retarded with DEX treatment, which was correlated with a significantly lower expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) mRNA in the liver (P =.006). Serum IL-8 and MCP-1 levels were also significantly down-regulated with DEX treatment (P = 0.008).

Conclusions: Glucocorticoid treatment is effective in modulating IL-8 and MCP-1 expression and ameliorating inflammatory cell infiltration in rat liver with bacterial cholangitis and cholestasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Infections / drug therapy
  • Bacterial Infections / metabolism*
  • Biliary Atresia / drug therapy
  • Biliary Atresia / surgery
  • Chemokine CCL2 / metabolism*
  • Cholangitis / drug therapy
  • Cholangitis / etiology
  • Cholangitis / metabolism*
  • Cholestasis / complications
  • Cholestasis / drug therapy
  • Cholestasis / metabolism
  • Dexamethasone / pharmacology*
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Down-Regulation
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Interleukin-8 / metabolism*
  • Liver / metabolism
  • Male
  • Postoperative Complications / drug therapy
  • Postoperative Complications / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Chemokine CCL2
  • Glucocorticoids
  • Interleukin-8
  • Dexamethasone