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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.

Background and Objectives: Previous studies have suggested that long-term β-blocker therapy before sepsis is associated with reduced mortality. Sepsis-associated coagulopathy (SAC) remains a common complication in patients with sepsis and is associated with increased mortality. Adrenergic pathways are involved in the regulation of the coagulation system. Pre-existing long-term β-blocker therapy may have potentially beneficial effects on SAC and has yet to be well characterized. We aimed to assess the potential association between pre-existing long-term β-blocker therapy and the outcomes of patients with SAC. Materials and Methods: This study retrospectively screened the clinical data of adult patients with SAC admitted to the Intensive Care Unit (ICU) and respiratory ICU between May 2020 and October 2022. Patients with SAC who took any β-blocker for at least one year were considered pre-existing long-term β-blocker therapy. All enrolled patients were followed up for 28 days or until death. Results: Among the 228 SAC patients, 48 received long-term β-blocker therapy before septic episodes. Pre-existing long-term β-blocker therapy was associated with reduced vasopressor requirements and a decreased 28-day mortality (log-rank test: p = 0.041). In particular, long-term β-blocker therapy was related to substantially lower D-dimer levels and a trend of improved activated partial thromboplastin time in patients with SAC during initial ICU admission. Multivariable regression analysis showed that long-term β-blocker therapy was significantly and independently associated with a 28-day mortality among patients with SAC (adjusted odds ratio, 0.55; 95% confidence interval, (0.32–0.94); p = 0.030). Conclusions: Pre-existing long-term β-blocker therapy might be associated with reduced vasopressor requirements and a decreased 28-day mortality among patients with SAC, providing evidence for the protective effect of β-blockers against SAC in managing sepsis.

Background Persistent immunosuppression characterized by immune cells apoptosis and T- lymphocyte subsets imbalance, occurs in septic patients with poor outcomes. Recent studies reported that Esmolol improved survival in septic shock via modulating immune responses. We hypothesized Esmolol alleviate sepsis-induced immunosuppression by regulating immune cell apoptosis and differentiation and sought to investigate the potential mechanisms and optimal dose. Methods Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (Esmolol:5mg.kg− 1.h− 1) and CLP + E-18 (Esmolol:18mg.kg− 1.h− 1) group. Another 8 rats were under sham operation. 18 hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and circulating T-lymphocyte subsets counts were determined by flow cytometry, protein expressions of p-Akt, Bcl-2, cleaved Caspase-3 and p-Erk1/2 were determined by western blot and immunohistochemistry. mRNA and protein expressions of β1-adrenoreceptors were evaluated by quantitative real-time PCR and immunohistochemistry. Results CLP induced tachycardia, hypotension, hyperlactatemia and multiple organ injuries. Infusion of Esmolol at 5mg.kg− 1.h− 1 didn't reduce heart rate, but improved mean arterial pressure, lactatemia and multiple organ injuries, decreased circulating T-lymphocyte apoptosis and the ratio of T help 2 cells and T help 1 cells, unregulated p-Akt and Bcl-2 expression and down-regulated cleaved Caspase-3 and p-Erk1/2 expression. Conclusions Esmolol without heart rate reduction attenuated sepsis-induced immunosuppression by preventing T-lymphocytes from apoptosis through regulating Akt/Bcl-2/Caspase-3 pathway and reducing naive CD4+ T cells differentiation to T help 2 cell through inhibiting Erk1/2 activation. Esmolol may be a potential immune regulator in septic shock.