Infection by gram-negative organisms via the biliary route results in greater mortality than portal venous infection

D. Rohan Jeyarajah, Mariusz L. Kielar, Nicole Frantz, Guy Lindberg, Christopher Y. Lu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Cholangitis requires bile duct obstruction and infection. Patients with cholangitis are often more affected than those with infections that reach the liver through the portal vein. We will attempt to study the influences of (i) route of entry and (ii) presence of bile duct obstruction on hepatic infection. C57BL/6 mice received injections of Escherichia coli or lipopolysaccharide into the obstructed bile duct or portal vein and were monitored for survival. Livers were assayed for bacteria, and cytokine mRNA was measured. In order to examine the effect of biliary obstruction on hepatic infection, animals were subjected to bile duct ligation 1 day prior to portal vein injection and were monitored for survival. The 50% lethal dose (LD50) for E. coli injected into the bile duct was 50 CFU/animal; the LD50 for E. coli injected into the portal vein was 5 × 107 CFU/animal. Initial hepatic delivery of bacteria was equivalent 1 h after injection into the bile duct or portal vein. However, by 24 h, a significantly greater amount of bacteria was recovered from the livers of the bile duct-injected group. Interleukin 10 (IL-10) and IL-1RA mRNA was expressed at greater levels in the bile duct-injected group. Prior bile duct ligation followed by portal vein injection resulted in a higher incidence of death than when sham operation was performed prior to portal vein injection. Our data suggest that the increased mortality from cholangitis, compared with that from other hepatic infections, is related to the different route of delivery of pathogen and the maladaptive response (possibly involving IL-10 and IL-1RA) to biliary obstruction itself.

Original languageEnglish (US)
Pages (from-to)664-669
Number of pages6
JournalClinical and Diagnostic Laboratory Immunology
Volume10
Issue number4
DOIs
StatePublished - Jul 2003

Fingerprint

Portal Vein
Bile Ducts
Ducts
Mortality
Liver
Cholangitis
Infection
Lethal Dose 50
Injections
Cholestasis
Escherichia coli
Bacteria
Animals
Interleukin-10
Ligation
Messenger RNA
Survival
Inbred C57BL Mouse
Lipopolysaccharides
Pathogens

ASJC Scopus subject areas

  • Microbiology (medical)
  • Immunology and Allergy
  • Clinical Biochemistry
  • Immunology

Cite this

Infection by gram-negative organisms via the biliary route results in greater mortality than portal venous infection. / Jeyarajah, D. Rohan; Kielar, Mariusz L.; Frantz, Nicole; Lindberg, Guy; Lu, Christopher Y.

In: Clinical and Diagnostic Laboratory Immunology, Vol. 10, No. 4, 07.2003, p. 664-669.

Research output: Contribution to journalArticle

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abstract = "Cholangitis requires bile duct obstruction and infection. Patients with cholangitis are often more affected than those with infections that reach the liver through the portal vein. We will attempt to study the influences of (i) route of entry and (ii) presence of bile duct obstruction on hepatic infection. C57BL/6 mice received injections of Escherichia coli or lipopolysaccharide into the obstructed bile duct or portal vein and were monitored for survival. Livers were assayed for bacteria, and cytokine mRNA was measured. In order to examine the effect of biliary obstruction on hepatic infection, animals were subjected to bile duct ligation 1 day prior to portal vein injection and were monitored for survival. The 50{\%} lethal dose (LD50) for E. coli injected into the bile duct was 50 CFU/animal; the LD50 for E. coli injected into the portal vein was 5 × 107 CFU/animal. Initial hepatic delivery of bacteria was equivalent 1 h after injection into the bile duct or portal vein. However, by 24 h, a significantly greater amount of bacteria was recovered from the livers of the bile duct-injected group. Interleukin 10 (IL-10) and IL-1RA mRNA was expressed at greater levels in the bile duct-injected group. Prior bile duct ligation followed by portal vein injection resulted in a higher incidence of death than when sham operation was performed prior to portal vein injection. Our data suggest that the increased mortality from cholangitis, compared with that from other hepatic infections, is related to the different route of delivery of pathogen and the maladaptive response (possibly involving IL-10 and IL-1RA) to biliary obstruction itself.",
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