Stellate Ganglion Block Improves the Proliferation and Function of Splenic CD4 + T Cells Through Inhibition of Posthemorrhagic Shock Mesenteric Lymph–Mediated Autophagy

Abstract

Background and objectiveSevere hemorrhagic shock leads to excessive in ammation 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) signi cantly normalized these indicators. In contrast, administration of autophagy agonist rapamycin (RAPA) or intravenous injection of PHSML inhibited the bene cial 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.

Effect of ultrasound-guided stellate ganglion block on inflammatory cytokines and postoperative recovery after partial hepatectomy: a randomised clinical trial

“…CRP in group S was significantly lower than that in group N on the sixth day after surgery, and there was no statistical difference when IL-6 reached its peak, which may be related to factors such as the longer delay difference in CRP change and the effect of liver resection on liver release of CRP. In terms of the inflammatory response, Ying Li et al found that stellate ganglion block could increase CD4 + T cell activity and decreased IL-2, IL-4, and TNF- stimulated TIPE2 production, hence increasing rat survival after severe hemorrhagic shock [ 6 ]. In 2020, Eugene Lipov et al put forward a hypothesis and gave some evidence to show that stellate ganglion block may regulate immune inflammation by regulating sympathetic innervation of primary (thymus, bone marrow) and secondary immune organs (such as the spleen, lymph nodes, and mucosa-associated lymphoid tissues), and it finally inhibits the production of pro-inflammatory cytokines (like IL-1, IL-6, TNF-α, etc.)…”

Estrogen Alleviates Posthemorrhagic Shock Mesenteric Lymph-Mediated Lung Injury Through Autophagy Inhibition

“…The surgery was carried out under inhalation anesthesia in all rats as previous described (20,21). After surgical procedures, the inhalation anesthesia was removed.…”

Innate immunity and immunotherapy for hemorrhagic shock

“…Previous studies have shown that stellate ganglion block (SGB), a standard method of blocking sympathetic nerves, can reduce intestinal barrier dysfunction and prolong the survival time in the HS rat model ( 159 ). The latest research shows that SGB administration significantly normalized the population of CD4 + T cells and the level of IL-2, IL-4, and TNFα-induced protein 8 like 2 (TIPE2) in the development of HS ( 146 ).…”