β-Adrenergic blockade during systemic inflammation: Impact on cellular immune functions and survival in a murine model of sepsis☆

Summary Aim of the study Adrenergic immuno-modulation mediated by β-adrenergic receptors has been demonstrated. Pharmacological blockade of β-adrenergic receptors is a therapeutic intervention frequently used in critically ill patients. The effect of β-adrenergic blockade on cellular immune functions in a critical illness, such as polymicrobial sepsis, has not been investigated. Methods Male NMRI-mice were subjected to sham operation or to sepsis (caecal ligation and puncture, CLP) following administration of either the non-selective β-adrenergic antagonist propranolol (0.5 mg/kg s.c. every 12 h in 1 ml vehicle) or saline 0.9% (1 ml s.c. every 12 h). Mice were kept in metabolic cages and were sacrificed 48 h after induction of sepsis. Survival rate, clinical situation (body weight and temperature, fluid and food intake, urine output), and immunological variables (splenocyte proliferation, apoptosis, and IFN-γ and IL-6 release) were determined. Results Administration of propranolol in septic mice increased the splenocyte apoptosis rate, reduced the proliferative capacity of splenocytes, and modulated cellular cytokine release (IL-6, IFN-γ). This was paralleled by a higher loss of body weight and temperature, and a decreased urine output. Furthermore, treatment with propranolol increased the sepsis-induced lethality from 47% up to 68%, respectively. Conclusion β-Adrenergic blockade was accompanied by alterations of cellular immune functions, a deterioration in the clinical situation and a reduced survival in a murine model of sepsis. These data demonstrate the potential immuno-modulatory effects of β-adrenergic antagonists.