β-adrenergic receptor-dependent and -independent stimulation of adenylate cyclase is impaired during severe sepsis in humans

摘要: Objectives: a) To investigate the functional consequences of sepsis on β-adrenergic signal transduction in human circulating lymphocytes; b) to appreciate sepsis-associated catecholamine and cytokine release. Design: Experimental, comparative study. Setting: Research laboratory a university hospital. Subjects: Healthy controls (n = 10); critically ill patients who were not septic 7); with severe or shock 11). Measurements main results: Experiments carried out using freshly isolated peripheral blood mononuclear cells (PBMC). We measured receptor (βAR) number affinity, intracellular cAMP content at baseline after pharmacological stimulation each component β -adrenergic complex: βAR isoproterenol, Gs-protein sodium fluoride (NaF), adenylate cyclase forskolin. Catecholamine (adrenaline, noradrenaline) (TNFα, IL-1α, IL-1β, IL-6) serum levels measured. In both non-septic we observed similar 40 % down-regulation βARs compared controls, reduced basal isoproterenol-stimulated accumulation (p < 0.05). The production elicited by NaF forskolin was lower than 0.01). Forskolin-stimulated significantly it ones 0.001). concentrations increased two patient groups without any significant difference. Elevated detected 45 (versus 14 p Conclusions: Patients presenting have extended postreceptor defects transduction. This finding suggests heterologous desensitization stimulation.