Beta-adrenergic modulation of human type-1/type-2 cytokine balance.
BACKGROUND
Neuroendocrine mediators are increasingly recognized as immunomodulatory agents. Lymphocytes and monocytes express receptors for a variety of neuroendocrine mediators, including catecholamines. It has been reported that beta-adrenergic agonists decrease IFN-gamma production, with varying effects on IL-4 and IL-5 production.


OBJECTIVE
Our purpose was to determine the effects of catecholamines (including beta-adrenergic agonists) on the type-1/type-2 cytokine balance in tetanus-stimulated human PBMCs.


METHODS
Human PBMCs were stimulated with tetanus in the presence of epinephrine (EPI), norepinephrine, or terbutaline. IFN-gamma, IL-4, IL-5, and IL-10 levels in the supernatants were determined by ELISA.


RESULTS
PBMCs stimulated in the presence of EPI produced decreased levels of IFN-gamma and increased levels of IL-10, IL-4, and IL-5. A small decrease in IFN-gamma production and an increase in IL-10, IL-4, and IL-5 production were also observed with norepinephrine. Terbutaline induced similar alterations in the type-1/type-2 cytokine balance compared with EPI, indicating that the beta(2)adrenergic receptor is involved in these cytokine alterations. Furthermore, these cytokine alterations were blocked by propranolol. Finally, IL-12p70 prevented the cytokine alterations, suggesting that the mechanism of beta-adrenergic-induced cytokine alterations involves a decrease in IL-12.


CONCLUSIONS
beta-Adrenergic agonists induce a shift in the human type-1/type-2 cytokine balance toward a type-2 response. These data provide a potential mechanism to explain the paradoxical increase in asthma morbidity and mortality associated with the chronic use of scheduled dosing of short-acting beta-adrenergic agonists.
Agarwal
S K
SK
Division of Allergy and Clinical Immunology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Marshall
G D
GD
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D002478:Cells, Cultured; D016207:Cytokines / Q000145:classification* / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D011433:Propranolol; D013726:Terbutaline; D009638:Norepinephrine; D004837:Epinephrine