RESUMO
OBJECTIVES: Although cardiovascular benefits of ß 1 -adrenergic receptor blockade have been described in sepsis, little is known about its impact on the adaptive immune response, specifically CD4 T cells. Herein, we study the effects of ß 1 -adrenergic receptor modulation on CD4 T-cell function in a murine model of sepsis. DESIGN: Experimental study. SETTING: University laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: High-grade sepsis was induced by cecal ligation and puncture in wild-type mice (ß 1+/+ ) with or without esmolol (a selective ß 1 -adrenergic receptor blocker) or in ß 1 -adrenergic receptor knockout mice (ß 1-/- ). At 18 hours after surgery, echocardiography was performed with blood and spleen collected to analyze lymphocyte function. MEASUREMENTS AND MAIN RESULTS: At 18 hours, ß 1+/+ cecal ligation and puncture mice exhibited characteristics of high-grade sepsis and three surrogate markers of immunosuppression, namely decreased splenic CD4 T cells, reduced CD4 T-cell proliferation, and increased regulatory T lymphocyte cell proportions. Pharmacologic and genetic ß 1 -adrenergic receptor blockade reversed the impact of sepsis on CD4 T and regulatory T lymphocyte proportions and maintained CD4 T-cell proliferative capacity. ß 1 -adrenergic receptor blocked cecal ligation and puncture mice also exhibited a global decrease in both pro- and anti-inflammatory mediators and improved in vivo cardiovascular efficiency with maintained cardiac power index despite the expected decrease in heart rate. CONCLUSIONS: ß 1 -adrenergic receptor activation enhances regulatory T lymphocyte inhibitory function and thus contributes to sepsis-induced immunosuppression. This can be attenuated by ß 1 -adrenergic receptor blockade, suggesting a potential immunoregulatory role for this therapy in the management of sepsis.
Assuntos
Sepse , Linfócitos T Reguladores , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Animais , Modelos Animais de Doenças , Humanos , Terapia de Imunossupressão , Camundongos , Camundongos Endogâmicos C57BL , Sepse/tratamento farmacológicoRESUMO
PURPOSE: Factors associated with adverse outcomes in ICU patients with type II (T2DM) are poorly defined. The main goal of this study is to determine the impact of pre-existing T2DM on 90-day mortality post ICU admission. MATERIAL: Post-hoc analysis from the FROG-ICU cohort. All patients admitted to ICU who were ventilated and/or treated by a vasoactive agent for >24 h were included. Association between T2DM and 90-day mortality was analyzed in unmatched, and populations matched by propensity score (PS) method to balance confounders recorded before ICU admission. Analysis was performed in non-imputed and imputed datasets. RESULTS: 2002 patients were included, and 16% had a history of T2DM. The latter were at inclusion more severely ill (SAPSII score 51(39-67) vs 48(35-61), p < 0.0001; Charlson score 2(1-3) vs 0(0-2), p < 0.0001). In the unmatched cohort, T2DM patients had a higher 90-day risk of death compared to no-DM patients (HR 1.35(1.1-1.65)). The 90-day risk of death was not significantly different T2DM and no T2DM patients after PS matching (HR: 0.81 (0.56-1.18). Results were similar with the analysis performed on imputed datasets (pooled HR: 0.95 (0.69-1.30)). CONCLUSIONS: In the present study, T2DM was not associated with 90-day mortality post ICU admission.