Date of Award

2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology, Neurobiology and Anatomy

Abstract

Roughly half of burn patients that are hospitalized in the United States each year have detectable blood alcohol levels. Alcohol intoxication at the time of burn injury leads to worse outcomes, including longer hospital stays, increased rates of infection, and death. One of the severe consequences of intoxication and burn injury is the disruption of the gastrointestinal (GI) tract, which houses the largest reservoir of bacteria in the human body. Leakiness of the gut barrier can contribute to inflammation, infection, or sepsis from gut-derived microbes. Interleukin-27 (IL-27) is a cytokine that has shown some beneficial effects in other models of intestinal inflammation, however, its role in promoting gut function following acute intoxication and burn injury has not previously been studied. The overall objectives of this dissertation were to identify whether IL-27 production and receptor expression was disrupted in the intestine following injury, and whether IL-27 administration may protect the intestinal barrier following intoxication and burn injury. Our results demonstrate that IL-27 is reduced in the intestine following injury. Administration of IL-27 was able to increase proliferation of epithelial cells in in vitro organoid cultures and our in vivo animal model. Furthermore, it was able to increase gene expression of tight junction proteins, reduce inflammation and neutrophil infiltration in intestinal tissue, and finally, restore gut barrier integrity and transit. Collectively, our results demonstrate a novel role for IL-27 in intoxication and burn injuries, and in particular for maintenance of the intestinal barrier. IL-27 not only promotes proliferation of intestinal epithelial cells and gene expression of tight junction proteins, but reduced inflammation in intestinal tissue. Together, these effects contributed to reduce gut leakiness and restore gut transit following alcohol and burn injury.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Saturday, October 07, 2023

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