Literature DB >> 15249727

Adrenergic modulation of survival and cellular immune functions during polymicrobial sepsis.

Reiner Oberbeck1, Daniel Schmitz, Klaus Wilsenack, Marc Schüler, Birthe Pehle, Manfred Schedlowski, Michael S Exton.   

Abstract

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. Copyright 2004 S. Karger AG, Basel

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Year:  2004        PMID: 15249727     DOI: 10.1159/000078439

Source DB:  PubMed          Journal:  Neuroimmunomodulation        ISSN: 1021-7401            Impact factor:   2.492


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