The sympathetic nervous system mechanism of exendin-4 in respect of modulating T cell-mediated immune response to severe burns in mice / 中华急诊医学杂志

ABSTRACT

Objective To investigate the potential effect of glucagon-like peptide-1 (GLP-1) analogue exendin-4 (Ex-4) on immune function of T lymphocytes via neuroendocrine modulation mechanism in mice following severe burns.Methods Male BALB/C mice were randomly (ramdam number) divided into thermal injury group (n =50) and sham-thermal group (n =30).The thermal injury model was made by exposing the back skin of 15％ total body surface area (TBSA) to 95 ℃ water for 7 seconds,while in sham-thermal model the mice were immersed in 37 ℃ water instead.The expression of GLP-1 receptor (GLP-1 R) was determined in sorted CM + T cells from normal mice by immunofluorescence method.In ex vivo experiment,the mice were sacrificed at 24 h post-bum,then the mononuclear cells (MNC) from spleen were separated from both groups and cultured in RMPI 1640 with 10％ FCS (fetal calf serum) in presence of ConA (concanavalin A,5 μg/mL).Cells were pretreated with catecholamine receptor antagonist propranolol (prop) for 1 hour,followed by consecutive dose of Ex-4 for another 48 h.In in vivo experiment,prop (30 mg/kg) was i.p.injected 30 minutes before thermal injury,then Ex-4 (2.4 nmol/kg) was injected i.p.immediately after scalding.Mice were sacrificed at 6 h and 24 h after thermal injury,then the serum and the spleens were collected.Results GLP-1R was expressed on splenic CD4 + T cells from normal micc.Ex-4 exerted no marked effect on the functions of T cells in terms of proliferation and IL-2 secretion at all doses examined ex vivo,which was not affected by pretreatment with prop.In vivo,T cell functions were suppressed by Ex-4 in thermal mice (P ＜ 0.05),but was restored by pretreatment with prop.Regardless of ex vivo or in vivo,Ex-4 could induce T cells switched to Th2 response (P ＜ 0.05).Moreover,the Th2 switch by Ex-4 was greatly potentiated by prop intervention in thermal mice in vivo other than ex vivo.Norepinephrine level was increased and epinephrine was decreased by Ex-4 in thermal mice.Both norepinephrine and epinephrine levels were obviously enhanced by pretreatment with prop.Conclusions Ex-4 can inhibit the proliferation and IL-2 secretion of splenic T lymphocytes through the sympathetic nervous system,however,it might induce Th2 switch from Th cells by acting directly on GLP-1R.