beta-Adrenergic blockade during systemic inflammation: impact on cellular immune functions and survival in a murine model of sepsis.
OBJECTIVE
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.


CONCLUSIONS
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.
Schmitz
Daniel
D
Department Trauma Surgery, University Hospital, University Duisburg-Essen, Essen, Germany.
Wilsenack
Klaus
K
Lendemanns
Sven
S
Schedlowski
Manfred
M
Oberbeck
Reiner
R
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects* / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007111:Immunity, Cellular / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D011433:Propranolol / Q000494:pharmacology*; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D011433:Propranolol