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A Role for Corticosterone in Impaired Intestinal Immunity and Barrier Function in a Rodent Model of Acute Alcohol Intoxication and Burn Injury

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Abstract

Alcohol (EtOH) intoxication and burn injury independently activate hypothalamic–pituitary–adrenal (HPA) axis, and glucocorticoids, the end product of the HPA axis, play a role in shaping the immune response under those conditions. By utilizing a rat model of acute EtOH intoxication and burn injury, studies in our laboratory have investigated the role of corticosterone (i.e., glucocorticoids in rodents) in altered intestinal immunity and barrier function following a combined insult of EtOH and burn injury. Results from these studies suggest that EtOH intoxication prior to burn injury augments corticosterone release, which in turn suppresses intestinal T cell function by inhibiting mitogen-activated protein kinase (i.e., p38 and ERK) pathway. Furthermore, we found that corticosterone does not directly alter the intestinal barrier function; rather, it up-regulates interleukin-18, which then directly or indirectly contributes to impaired intestinal barrier function. The loss of intestinal immunity/barrier function may result in increased bacterial translocation and thereby contribute to postinjury pathogenesis, leading to sepsis and organ dysfunction in burn patients as well as in patients with a history of EtOH intoxication.

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Acknowledgements

Findings from our laboratory reported in this article were generated during the support from NIH (NIAAA) R21AA12901 (MAC). The authors would like to thank Ms. Bobbi Smith for editing.

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Authors and Affiliations

  1. Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

    Mashkoor A. Choudhry, Xiaoling Li & Irshad H. Chaudry

  2. Center for Surgical Research, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall, Room G094, Birmingham, AL, 35294-0019, USA

    Mashkoor A. Choudhry

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  1. Mashkoor A. Choudhry
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  2. Xiaoling Li
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  3. Irshad H. Chaudry
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Correspondence to Mashkoor A. Choudhry.

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Choudhry, M.A., Li, X. & Chaudry, I.H. A Role for Corticosterone in Impaired Intestinal Immunity and Barrier Function in a Rodent Model of Acute Alcohol Intoxication and Burn Injury. Jrnl Neuroimmune Pharm 1, 428–434 (2006). https://doi.org/10.1007/s11481-006-9031-5

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