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Although glucagon-like peptide 1- (GLP-1-) based therapy of hyperglycemia in burn injury has shown great potential in clinical trials, its safety is seldom evaluated. We hypothesize that exendin-4, a GLP-1 analogue, might affect the immune response via the activation of the sympathetic nervous system in burn injury.<jats:italic>Methods<\/jats:italic>. Male Balb\/c mice were subjected to sham or thermal injury of 15% total body surface area. Exendin-4 on T cell function<jats:italic>in vitro<\/jats:italic>was examined in cultured splenocytes in the presence of<jats:italic>\u03b2<\/jats:italic>-adrenoceptor antagonist propranolol (1\u2009nmol\/L) or GLP-1R antagonist exendin (9-39) (1\u2009<jats:italic>\u03bc<\/jats:italic>mol\/L), whereas its<jats:italic>in vivo<\/jats:italic>effect was determined by i.p. injection of exendin-4 (2.4\u2009nmol\/kg) in mice. To further elucidate the sympathetic mechanism, propranolol (30\u2009mg\/kg) or vehicle was applied 30\u2009min prior to injury.<jats:italic>Results<\/jats:italic>. Although the exacerbated burn-induced mortality by exendin-4 was worsened by propranolol pretreatment, the inhibition of T cell proliferation by exendin-4<jats:italic>in vitro<\/jats:italic>could be restored by propranolol instead of exendin (9-39). However, a Th2 switch by exendin-4<jats:italic>in vitro<\/jats:italic>could only be reversed by exendin (9-39). Likewise, the inhibition of splenic T cell function and NFAT activity by exendin-4<jats:italic>in vivo<\/jats:italic>was restored by propranolol. By contrast, the increased splenic NF-<jats:italic>\u03ba<\/jats:italic>B translocation by exendin-4<jats:italic>in vivo<\/jats:italic>was potentiated by propranolol in sham mice but suppressed in burn mice. Accordingly, propranolol abrogated the heightened inflammatory response in the lung and the accelerated organ injuries by exendin-4 in burn mice. On the contrary, a Th2 switch and higher serum levels of inflammatory mediators by exendin-4 were potentiated by propranolol in burn mice. Lastly, exendin-4 raised serum stress hormones which could be remarkably augmented by propranolol.<jats:italic>Conclusions<\/jats:italic>. Exendin-4 suppresses T cell function and promotes organ inflammation through the activation of the sympathetic nervous system, while elicits Th2 switch via GLP-1R in burn injury.<\/jats:p>","DOI":"10.1155\/2019\/2750528","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T23:31:52Z","timestamp":1547767912000},"page":"1-16","source":"Crossref","is-referenced-by-count":4,"title":["Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System"],"prefix":"10.1155","volume":"2019","author":[{"given":"Xiao-Jing","family":"Ji","sequence":"first","affiliation":[{"name":"Trauma Research Center, Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Wei","family":"Hao","sequence":"additional","affiliation":[{"name":"Trauma Research Center, Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, 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