LOW DOSE OF ESMOLOL ATTENUATES SEPSIS-INDUCED IMMUNOSUPPRESSION VIA MODULATING T-LYMPHOCYTE APOPTOSIS AND DIFFERENTIATION.
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 05 2023
01 05 2023
Historique:
medline:
24
4
2023
pubmed:
1
3
2023
entrez:
28
2
2023
Statut:
ppublish
Résumé
Background: Immunosuppression caused by immune cell apoptosis and an imbalance of T helper 2 cells (T H 2) and T helper 1 cells (T H 1), is associated with poor outcomes in septic patients. Esmolol was reported to improve survival by modulating immune responses in septic shock. Whether esmolol could alleviate sepsis-induced immunosuppression and the optimal dose are unclear. Methods: Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (esmolol: 5 mg·kg -1 ·h -1 ) and CLP + E-18 (esmolol: 18 mg·kg -1 ·h -1 ) groups. Eight rats were underwent sham operation. Eighteen hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and T-lymphocyte subsets counts were determined by flow cytometry, and the expression of p-Akt, Bcl-2, cleaved Caspase-3, and p-Erk1/2 in splenic CD4 + T-lymphocytes was determined by western blot and immunohistochemistry. β 1 -Adrenoreceptor expressions were evaluated using real-time polymerase chain reaction and immunohistochemistry. Results: Cecal ligation and puncture induced tachycardia, hypotension, hyperlactatemia, and multiple organ injury. Heart rate was unchanged in the CLP + E-5 group but decreased in the CLP + E-18 group. Hypotension, lactatemia, and multiple organ injuries were improved only in the CLP + E-5 group. T-lymphocyte apoptosis and T H 2/T H 1 ratio was decreased in CLP + E-5 but not in CLP + E-18. p-Akt and Bcl-2 expressions were increased, while cleaved Caspase-3 and p-Erk1/2 expressions were decreased in CLP + E-5. β 1 -Adrenoreceptor expressions were unchanged in both CLP + E-5 and CLP + E-18 groups. Conclusions: Low dose of esmolol reduced T-lymphocyte apoptosis and restored T H 2/T H 1 ratio in septic shock. Esmolol might modulate Akt/Bcl-2/Caspase-3 pathway to relieve T-lymphocyte apoptosis and inhibit Erk1/2 activity to decrease T H 0 differentiation to T H 2. Esmolol may be a potential immunoregulator of septic shock.
Identifiants
pubmed: 36852973
doi: 10.1097/SHK.0000000000002104
pii: 00024382-202305000-00012
pmc: PMC10125111
doi:
Substances chimiques
esmolol
MDY902UXSR
Caspase 3
EC 3.4.22.-
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Proto-Oncogene Proteins c-bcl-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
771-778Informations de copyright
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.
Déclaration de conflit d'intérêts
The authors report conflict of interests.
Références
Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA . 2016;315(8):801–810.
Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol . 2013;13(12):862–874.
Delano MJ, Ward PA. The immune system's role in sepsis progression, resolution, and long-term outcome. Immunol Rev . 2016;274(1):330–353.
Boomer JS, To K, Chang KC, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA . 2011;306(23):2594–2605.
Ferguson NR, Galley HF, Webster NR. T helper cell subset ratios in patients with severe sepsis. Intensive Care Med . 1999;25(1):106–109.
Suzuki T, Morisaki H, Serita R, et al. Infusion of the beta-adrenergic blocker esmolol attenuates myocardial dysfunction in septic rats. Crit Care Med . 2005;33(10):2294–2301.
Morelli A, Ertmer C, Westphal M, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA . 2013;310(16):1683–1691.
Morelli A, Singer M, Ranieri VM, et al. Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study. Intensive Care Med . 2016;42(10):1528–1534.
Kimmoun A, Louis H, Al Kattani N, et al. β 1 -Adrenergic inhibition improves cardiac and vascular function in experimental septic shock. Crit Care Med . 2015;43(9):e332–e340.
Wei C, Louis H, Schmitt M, et al. Effects of low doses of esmolol on cardiac and vascular function in experimental septic shock. Crit Care . 2016;20(1):407.
Durand M, Hagimont E, Louis H, et al. The β 1 -adrenergic receptor contributes to sepsis-induced immunosuppression through modulation of regulatory T-cell inhibitory function. Crit Care Med . 2022;50(9):e707–e718.
Vassilatis DK, Hohmann JG, Zeng H, et al. The G protein–coupled receptor repertoires of human and mouse. Proc Natl Acad Sci U S A . 2003;100(8):4903–4908.
Sun L, Ye RD. Role of G protein–coupled receptors in inflammation. Acta Pharmacol Sin . 2012;33(3):342–350.
Zhang HUA, Xiong Z, Wang J, et al. Glucagon-like peptide-1 protects cardiomyocytes from advanced oxidation protein product-induced apoptosis via the PI3K/Akt/Bad signaling pathway. Mol Med Rep . 2016;13(2):1593–1601.
Qi Z, Wang R, Liao R, et al. Neferine ameliorates sepsis-induced myocardial dysfunction through anti-apoptotic and antioxidative effects by regulating the PI3K/AKT/mTOR signaling pathway. Front Pharmacol . 2021;12:706251.
Zheng J, Shen H, Xiong Y, et al. The beta1-adrenergic receptor mediates extracellular signal-regulated kinase activation via Galphas. Amino Acids . 2010;38(1):75–84.
Tripathi P, Sahoo N, Ullah U, et al. A novel mechanism for ERK-dependent regulation of IL4 transcription during human T H 2-cell differentiation. Immunol Cell Biol . 2012;90(7):676–687.
Ansel KM, Djuretic I, Tanasa B, et al. Regulation of T H 2 differentiation and Il4 locus accessibility. Annu Rev Immunol . 2006;24:607–656.
Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nat Rev Immunol . 2002;2(12):933–944.
Wei C, Al Kattani N, Louis H, et al. If channel inhibition with ivabradine does not improve cardiac and vascular function in experimental septic shock. Shock . 2016;46(3):297–303.
Khodir AE, Samra YA, Said E. A novel role of nifuroxazide in attenuation of sepsis-associated acute lung and myocardial injuries; role of TLR4/NLPR3/IL-1β signaling interruption. Life Sci . 2020;256:117907.
Principe DR, Diaz AM, Torres C, et al. TGFbeta engages MEK/ERK to differentially regulate benign and malignant pancreas cell function. Oncogene . 2017;36(30):4336–4348.
Cao C, Yu M, Chai Y. Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis. Cell Death Dis . 2019;10(10):782.
Ackland GL, Yao ST, Rudiger A, et al. Cardioprotection, attenuated systemic inflammation, and survival benefit of beta1-adrenoceptor blockade in severe sepsis in rats. Crit Care Med . 2010;38(2):388–394.
Mori K, Morisaki H, Yajima S, et al. Beta-1 blocker improves survival of septic rats through preservation of gut barrier function. Intensive Care Med . 2011;37(11):1849–1856.
Ibrahim-Zada I, Rhee P, Gomez CT, et al. Inhibition of sepsis-induced inflammatory response by β 1 -adrenergic antagonists. J Trauma Acute Care Surg . 2014;76(2):320–327; discussion 327–8.
Shao R, Fang Y, Yu H, et al. Monocyte programmed death ligand-1 expression after 3–4 days of sepsis is associated with risk stratification and mortality in septic patients: a prospective cohort study. Crit Care . 2016;20(1):124.
Stolk RF, Kox M, Pickkers P. Noradrenaline drives immunosuppression in sepsis: clinical consequences. Intensive Care Med . 2020;46(6):1246–1248.
Jiang JL, Peng YP, Qiu YH, et al. Adrenoreceptor-coupled signal-transduction mechanisms mediating lymphocyte apoptosis induced by endogenous catecholamines. J Neuroimmunol . 2009;213(1–2):100–111.
Xue M, Xie J, Liu L, et al. Early and dynamic alterations of T H 2/T H 1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study. J Transl Med . 2019;17(1):57.
Xue M, Tang Y, Liu X, et al. Circulating T H 1 and T H 2 subset accumulation kinetics in septic patients with distinct infection sites: pulmonary versus nonpulmonary. Mediators Inflamm . 2020;2020:8032806.
Noben-Trauth N, Hu-Li J, Paul WE. Conventional, naive CD4+ T cells provide an initial source of IL-4 during T H 2 differentiation. J Immunol . 2000;165(7):3620–3625.