Bench-to-bedside review: β-Adrenergic modulation in sepsis

Sepsis, despite recent therapeutic progress, still carries unacceptably high mortality rates. The adrenergic system, a key modulator of organ function and cardiovascular homeostasis, could be an interesting new therapeutic target for septic shock. beta-Adrenergic regulation of the immune function in sepsis is complex and is time dependent. However, beta(2) activation as well as beta(1) blockade seems to downregulate proinflammatory response by modulating the cytokine production profile. beta(1) blockade improves cardiovascular homeostasis in septic animals, by lowering myocardial oxygen consumption without altering organ perfusion, and perhaps by restoring normal cardiovascular variability. beta-Blockers could also be of interest in the systemic catabolic response to sepsis, as they oppose epinephrine which is known to promote hyperglycemia, lipid and protein catabolism. The role of beta-blockers in coagulation is less clear cut. They could have a favorable role in the septic procoagulant state, as beta(1) blockade may reduce platelet aggregation and normalize the depressed fibrinolytic status induced by adrenergic stimulation. Therefore, beta(1) blockade as well as beta(2) activation improves sepsis-induced immune, cardiovascular and coagulation dysfunctions. beta(2) blocking, however, seems beneficial in the metabolic field. Enough evidence has been accumulated in the literature to propose beta-adrenergic modulation, beta(1) blockade and beta(2) activation in particular, as new promising therapeutic targets for septic dyshomeostasis, modulating favorably immune, cardiovascular, metabolic and coagulation systems.