title: Dose-dependent effects of ethanol and E. coli on gut permeability and cytokine production.
abstract: BACKGROUND
  The gut may prime inflammatory responses following shock/trauma insults. Ethanol (EtOH) use is common in trauma patients and may impair intestinal barrier function. We compared varying concentrations of EtOH on proinflammatory cytokine production of Caco2 cell monolayers and the resultant changes in barrier function. We hypothesized that even low concentrations of EtOH would cause significant cytokine release and barrier dysfunction in vitro.
  
  
  METHODS
  Confluent Caco2 cell monolayers were grown in a two-chamber culture system and exposed to varying concentrations of EtOH (0.1%, 0.5%, 1.0%, 1.5%, and 2.0%) with/without Escherichia coli C-25 (EC). Supernatants were collected and TNF and IL6 quantified by ELISA (pg/mL). Monolayer integrity was assessed by apoptosis and permeability measurements.
  
  
  RESULTS
  Caco2 production of TNF-alpha increased in a dose-dependent manner when incubated with increasing concentrations of EtoH. A synergistic effect was seen when E. coli was added to the apical chamber. A similar result was seen with the production of IL-6. A dose-dependent effect was also noted with EtOH with or without E. coli on apoptosis and permeability measurements.
  
  
  CONCLUSIONS
  In addition to alterations in gut permeability, increasing concentrations of ethanol have a synergistic effect with E. coli on Caco2 production of proinflammatory cytokines TNF and IL-6. The creation of a proinflammatory cytokine milieu with an altered barrier integrity may be a mechanism by which ethanol may increase septic complications in the injured patient.
authors.affiliation: Department of Surgery, Wayne State University, Detroit, Michigan 48201, USA. pamin@med.wayne.edu
authors.forename: Parth B
authors.initials: PB
authors.lastname: Amin
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Diebel
authors.forename: David M
authors.initials: DM
authors.lastname: Liberati
mesh_terms: D000230:Adenocarcinoma / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000472:pathogenicity*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol