Acute Ethanol Exposure Combined With Burn Injury Enhances IL-6 Levels in the Murine Ileum

Authors

  • Michael T. Scalfani,

    1. From the Department of Cell Biology, Neurobiology & Anatomy, Loyola University Medical Center, Maywood, Illinois (MTS, DMC, ELM, EJK, FAW); the Alcohol Research Program, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Department of Surgery, Loyola University Medical Center, Maywood, Illinois (EJK); and the Department of Anesthesiology (FAW), Loyola University Medical Center, Maywood, Illinois.
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  • David M. Chan,

    1. From the Department of Cell Biology, Neurobiology & Anatomy, Loyola University Medical Center, Maywood, Illinois (MTS, DMC, ELM, EJK, FAW); the Alcohol Research Program, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Department of Surgery, Loyola University Medical Center, Maywood, Illinois (EJK); and the Department of Anesthesiology (FAW), Loyola University Medical Center, Maywood, Illinois.
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  • Eva L. Murdoch,

    1. From the Department of Cell Biology, Neurobiology & Anatomy, Loyola University Medical Center, Maywood, Illinois (MTS, DMC, ELM, EJK, FAW); the Alcohol Research Program, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Department of Surgery, Loyola University Medical Center, Maywood, Illinois (EJK); and the Department of Anesthesiology (FAW), Loyola University Medical Center, Maywood, Illinois.
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  • Elizabeth J. Kovacs,

    1. From the Department of Cell Biology, Neurobiology & Anatomy, Loyola University Medical Center, Maywood, Illinois (MTS, DMC, ELM, EJK, FAW); the Alcohol Research Program, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Department of Surgery, Loyola University Medical Center, Maywood, Illinois (EJK); and the Department of Anesthesiology (FAW), Loyola University Medical Center, Maywood, Illinois.
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  • Fletcher A. White

    1. From the Department of Cell Biology, Neurobiology & Anatomy, Loyola University Medical Center, Maywood, Illinois (MTS, DMC, ELM, EJK, FAW); the Alcohol Research Program, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois (EJK, FAW); the Department of Surgery, Loyola University Medical Center, Maywood, Illinois (EJK); and the Department of Anesthesiology (FAW), Loyola University Medical Center, Maywood, Illinois.
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  • Funding for this study was provided by Illinois Excellence in Academic Medicine (FAW, EJK), Ralph and Marion C. Falk Medical Research Trust (EJK) and NIH R01 AA12034 (EJK) and NIH T32 AA13527 (EJK).

Reprint requests: Fletcher A. White, Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153; Fax: 708-216-6731; E-mail: fwhite@lumc.edu

Abstract

Background:  Recent studies suggest that ethanol use imposes a greater risk of trauma-associated intestinal injury than trauma alone. The initiating and regulatory factors for multiple organ dysfunction syndromes are not well defined, yet evidence points to the gut as a possible trigger of the systemic inflammatory cascade as well as a potential source of cytokines. In the current study, we hypothesized that ethanol administration would alter cytokine levels and intestinal infiltration by neutrophils within the ileum of mice exposed to burn injury (15% total body surface of dorsal skin).

Methods:  Ileal samples were collected for histological assessment, myeloperoxidase quantitation and the protein presence of tumor necrosis factor alpha (TNFα), interleukin (IL-) 6, macrophage inflammatory protein-2 (MIP-2; CXCL2) and the anti-inflammatory cytokine, IL-10. Additional ileal tissue samples were examined for localization of the IL-6 immunoreactivity.

Results:  We did not detect statistically significant cytokine/chemokine differences (MIP-2 and IL-10) between sham control and treatment conditions at either 2 or 24 hours. However, there was a significant decrease in TNFα at 24 hours in both burn injury alone and in combination with ethanol treatment conditions (p < 0.05). In addition, there was an increase in IL-6 levels at 24 hours in intestinal tissue obtained from mice subjected to a combination of acute ethanol and burn injury, compared to the mice receiving burn or sham injury (p < 0.001). Ileal homogenate increases in IL-6 at 24 hours were concurrent with decreased villus height in the ileum, but no discernable changes in neutrophil infiltration (myeloperoxidase activity levels) at either 2 or 24 hours. Additional immunocytochemical localization studies of ileal tissue revealed that there was a substantial increase of IL-6 in intestinal enterocytes subjected to both burn injury alone, or in combination with acute ethanol exposure.

Conclusions:  The present study suggests that acute ethanol exposure combined with burn injury enhances levels of IL-6 protein in the ileum. The enhanced levels of ileal IL-6 are likely due to enterocyte production of the cytokine.

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