AIM OF THE STUDY: Adrenergic immuno-modulation mediated by beta-adrenergic receptors has been demonstrated. Pharmacological blockade of beta-adrenergic receptors is a therapeutic intervention frequently used in critically ill patients. The effect of beta-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 beta-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-gamma 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-gamma). 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: beta-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 beta-adrenergic antagonists.
AIM OF THE STUDY: Adrenergic immuno-modulation mediated by beta-adrenergic receptors has been demonstrated. Pharmacological blockade of beta-adrenergic receptors is a therapeutic intervention frequently used in critically illpatients. The effect of beta-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 beta-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-gamma 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-gamma). 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: beta-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 beta-adrenergic antagonists.
Authors: Ioannis Barbas; Ioannis G Fatouros; Ioannis I Douroudos; Athanasios Chatzinikolaou; Yiannis Michailidis; Dimitrios Draganidis; Athanasios Z Jamurtas; Michalis G Nikolaidis; Charalabos Parotsidis; Anastasios A Theodorou; Ioannis Katrabasas; Konstantinos Margonis; Ioannis Papassotiriou; Kyriakos Taxildaris Journal: Eur J Appl Physiol Date: 2010-12-16 Impact factor: 3.078
Authors: Jennifer L Steiner; Kristen T Crowell; Scot R Kimball; Charles H Lang Journal: Am J Physiol Endocrinol Metab Date: 2015-10-20 Impact factor: 4.310