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THE SYNERGISTIC EFFECT OF ETHANOL AND SHOCK INSULTS ON CACO2 CYTOKINE PRODUCTION AND APOPTOSIS

Amin, Parth B.; Diebel, Lawrence N.; Liberati, David M.

doi: 10.1097/SHK.0b013e318157ec2e
Basic Science Aspects

Gut epithelial cells are important in orchestrating immunoinflammatory responses in the gut and may impact systemic immunocompetent cells after shock and trauma. Ethanol (EtOH) intoxication is an important etiological factor in trauma and may increase the likelihood of posttraumatic septic complications. Both EtOH and gut I/R impair intestinal barrier function. However, their combined effects on intestinal epithelial cell function and barrier integrity are unknown. Confluent Caco2 cell monolayers were grown in a two-chamber culture system and exposed to 0.1% EtOH and/or Escherichia coli C-25 under normoxic (21% O2) or hypoxia (5% O2) followed by reoxygenation (H/R). Apical and basal compartment supernatants were collected, and TNF and IL-6 were quantitated by enzyme-linked immunosorbent assay (picograms per milliliter). Caco2 cell integrity was indexed by apoptosis and monolayer permeability. TNF-α production by Caco2 cells are greatest when incubated with EtOH and then exposed to H/R group. The apical levels of TNF production are consistently higher than basal levels, although the trend toward increased cytokine production is similar in both compartments. IL-6 production by the Caco2 cell is also greatest when Caco2 cells incubated with EtOH undergoes H/R. Lastly, the findings in apoptosis mirror the data of the TNF production in the apical compartment. Ethanol and H/R have a synergistic effect on cytokine production and barrier dysfunction in this model. They may also contribute to increased infectious complications and posttraumatic organ failure.

Department of Surgery, Wayne State University/University Health Center, Detroit, Michigan

Received 4 Jun 2007; first review completed 14 Jun 2007; accepted in final form 31 Jul 2007

Address reprint requests to Parth B. Amin, MD, Dept. of Surgery, Wayne State University/University Health Center, 6-C, 4201 St. Antoine, Detroit, MI 48201. E-mail: pamin@med.wayne.edu.

©2008The Shock Society