Exendin-4 Exacerbates Burn-Induced Mortality in Mice by Switching to Th2 Response.

Introduction: To determine if Exendin-4 could be a therapeutic agent for burn-induced hyperglycemia.Materials and methods: Male Balb/c mice received a bolus of Exendin-4 intraperitoneally immediately after 15% total body surface area scald injury. Tail glucose levels were recorded and T-cell functions were analyzed at 4 h and 24 h postburn (pb). Pancreatic pathology was observed consecutively. The secretions of cytokines were detected in serum, spleen, and lung. Apoptosis of splenic CD3+ T-cells was examined by terminal deoxynucleotidyl trans-ferase-mediated dUTP nick-end labeling and flow cytometry.Results: Although Exendin-4 could attenuate burn-induced hyperglycemia in mice at 4 h pb, it accelerated their survival dose dependently with progressive depletion of splenocyte number. T-cell function underwent two-phasic changes following Exendin-4 treatment. Compared to placebo mice, T-cell from Exendin-4-treated mice was manifested with increased proliferation, while decreased IL-2 secretion and lower ratio of IL-4/IFN-gamma at 4 h pb. However, at 24 h pb, it showed decreased proliferation, while increased IL-2 secretion and higher ratio of IL-4/IFN-gamma. Exendin-4 could elicit higher circulating IL-6 and IL-10 levels at 4 h pb, which were pronounced in the lung at 24 h pb. In the meanwhile, severe inflammation could be found in the pancreas. At 24 h pb, the numbers of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling or caspase-3 positive cells and the apoptosis of CD3+ T-cells were significantly increased in the spleens of Exendin-4 mice relative to placebo mice.Conclusions: These data support a pathogenic role of Exendin-4 signaling during thermal injury, warning against its clinical application in acute insults.(c) 2022 Elsevier Inc. All rights reserved.