Document Detail

Adrenergic modulation of survival and cellular immune functions during polymicrobial sepsis.
MedLine Citation:
PMID:  15249727     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: An immunomodulatory effect of epinephrine has been reported that is supposed to be mediated via beta-adrenergic receptors. The effect of epinephrine and/or beta-adrenergic blockade on cellular immune functions during systemic inflammation has not yet been investigated. METHODS: Male NMRI mice were treated with either an infusion of epinephrine (0.05 mg/kg/h i.p.), administration of the nonselective beta-adrenoceptor antagonist propranolol (0.5 mg/kg s.c.), or a combination of epinephrine and propranolol after induction of a polymicrobial sepsis by cecal ligation and puncture. Forty-eight hours thereafter survival and cellular immune functions (splenocyte proliferation, splenocyte apoptosis and cytokine release, distribution of leukocyte subsets) were determined. RESULTS: Infusion of epinephrine did not affect lethality of septic mice but induced alterations of splenocyte apoptosis, splenocyte proliferation and IL-2 release and was associated with profound changes of circulating immune cell subpopulations. Treatment with propranolol augmented the epinephrine-induced increase of splenocyte apoptosis, did not affect the decrease of splenocyte proliferation and IL-2 release, augmented the release of IL-6 and antagonized the mobilization of natural killer cells observed in epinephrine-treated animals. Furthermore, these immunologic alterations were accompanied by a significant increase of sepsis-induced mortality. Coadministration of propranolol and epinephrine augmented the propranolol-induced changes of splenocyte apoptosis and IL-6 release and was associated with the highest mortality of septic mice. CONCLUSION: Epinephrine infusion modulated cellular immune functions during systemic inflammation without an impact on survival. A pharmacologic beta-adrenergic blockade partly augmented the epinephrine-induced immune alterations and was associated with a pronounced increase of mortality. This effect was further augmented by a combination of epinephrine infusion and beta-adrenergic blockade. These data indicate that adrenergic mechanisms modulate cellular immune functions and survival during sepsis, with these effects being mediated via alpha- and beta-adrenergic pathways.
Reiner Oberbeck; Daniel Schmitz; Klaus Wilsenack; Marc Schüler; Birthe Pehle; Manfred Schedlowski; Michael S Exton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroimmunomodulation     Volume:  11     ISSN:  1021-7401     ISO Abbreviation:  Neuroimmunomodulation     Publication Date:  2004  
Date Detail:
Created Date:  2004-07-13     Completed Date:  2004-10-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9422763     Medline TA:  Neuroimmunomodulation     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  214-23     Citation Subset:  IM    
Copyright Information:
Copyright 2004 S. Karger AG, Basel
Department of Trauma Surgery, University Hospital of Essen, Essen, Germany.
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MeSH Terms
Adrenergic beta-Antagonists / pharmacology
Apoptosis / drug effects,  immunology
Cell Division / drug effects,  immunology
Cytokines / drug effects,  immunology
Drug Synergism
Epinephrine / blood,  immunology*,  pharmacology
Immunity, Cellular / drug effects,  immunology*
Lymphocyte Activation / drug effects,  immunology
Lymphocytes / drug effects,  immunology
Neuroimmunomodulation / immunology*
Norepinephrine / blood,  immunology
Propranolol / pharmacology
Receptors, Adrenergic, beta / drug effects,  immunology*
Sepsis / drug therapy,  immunology*,  microbiology
Spleen / cytology,  drug effects,  immunology
Survival Rate
Sympathetic Nervous System / immunology*
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Cytokines; 0/Receptors, Adrenergic, beta; 51-41-2/Norepinephrine; 51-43-4/Epinephrine; 525-66-6/Propranolol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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