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. β-Adrenergic regulation of the immune function in sepsis is complex and is time dependent. However, β₂ activation as well as β₁ blockade seems to downregulate proinflammatory response by modulating the cytokine production profile. β₁ blockade improves cardiovascular homeostasis in septic animals, by lowering myocardial oxygen consumption without altering organ perfusion, and perhaps by restoring normal cardiovascular variability. β-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 β-blockers in coagulation is less clear cut. They could have a favorable role in the septic pro-coagulant state, as β₁ blockade may reduce platelet aggregation and normalize the depressed fibrinolytic status induced by adre-nergic stimulation. Therefore, β₁ blockade as well as β₂ activation improves sepsis-induced immune, cardiovascular and coagulation dysfunctions. β₂ blocking, however, seems beneficial in the metabolic field. Enough evidence has been accumulated in the literature to propose β- adrenergic modulation, β₁ blockade and β₂ activation in particular, as new promising therapeutic targets for septic dyshomeostasis, modulating favorably immune, cardiovascular, metabolic and coagulation systems.