Abstract
Background and objectiveSevere hemorrhagic shock leads to excessive inflammation and immune dysfunction, which resulted in high mortality related to mesenteric lymph return. Recent study showed that stellate ganglion block (SGB) increased survival rate in rats suffered hemorrhagic shock. However, whether SGB ameliorates immune dysfunction induced by hemorrhagic shock, it remains unknown. The aim of present study is therefore to verify the favorable effect of SGB on the proliferation and function of splenic CD4 + T cells isolated from rats underwent hemorrhagic shock, and investigate its mechanism focusing autophagy and PHSML.Materials and methodsMale rats underwent SGB or sham SGB pretreatment and conscious acute hemorrhage followed by resuscitation and multiple treatments. After three hours of resuscitation, splenic CD4 + T cells were isolated for the measurements of proliferation and cytokine production following stimulation with ConA in vitro. Furthermore, the CD4 + T cells isolated from normal rats were treated with post-hemorrhagic shock mesenteric lymph (PHSML) drained from rats treated with SGB or not. And the proliferation, cytokine production and autophagy biomarkers were detected.ResultsHemorrhagic shock reduced CD4 + T cells proliferation and function to produce interleukin (IL)-2, IL-4 and tumor necrosis factor-α-induced protein 8 like 2 (TIPE2). SGB pretreatment or administration of autophagy inhibitor 3-methyladenine (3-MA) significantly normalized these indicators. In contrast, administration of autophagy agonist rapamycin (RAPA) or intravenous injection of PHSML inhibited the beneficial effect of SGB on CD4 + T cells obtained from hemorrhagic shocked rats. Furthermore, PHSML incubation decreased the proliferation and cytokine production, increased LC3 II/I and Beclin-1 expressions, and reduced p-PI3K and p-Akt expressions of normal CD4 + T cells. More critically, these adverse effects of PHSML were abolished by 3-MA administration, as well as incubation with PHSML obtained from SGB treated rats.ConclusionsSGB improves splenic CD4 + T cells function following hemorrhagic shock, which is related to the inhibition of PHSML-mediated autophagy.
TBET‐expressing Th1 CD4
+
T cells accumulate in chronic lymphocytic leukaemia without affecting disease progression in Eµ‐TCL1 mice