Background: Neuroendocrine mediators are increasingly recognized as immunom
odulatory agents. Lymphocytes and monocytes express receptors for a variety
of neuroendocrine mediators, including catecholamines, It has been reporte
d that beta-adrenergic agonists decrease IFN-gamma production, with varying
effects on IL-4 and 1L-5 production.
Objective: Our purpose was to determine the effects of catecholamines (incl
uding beta-adrenergic agonists) on the type-1/type-2 cytokine balance in te
tanus-stimulated human PBMCs.
Method: Human PBMCs were stimulated with tetanus in the presence of epineph
rine (EPI), norepinephrine, or terbutaline, IFN-gamma, IL-4, IL-5, and IL-1
0 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 1L-5. A small decreas
e in IFN-gamma production and an increase in IL-10, IL-4, and IL-5 producti
on were also observed with norepinephrine. Terbutaline induced similar alte
rations in the type-1/type-2 cytokine balance compared with EPI, indicating
that the beta(2)adrenergic receptor is involved in these cytokine alterati
ons. Furthermore, these cytokine alterations were blocked by propranolol. F
inally, IL-12p70 prevented the cytokine alterations, suggesting that the me
chanism of beta-adrenergic-induced cytokine alterations involves a decrease
in IL-12.
Conclusion: beta-Adrenergic agonists induce a shift in the human type-1/typ
e-2 cytokine balance toward a type-2 response. These data provide a potenti
al mechanism to explain the paradoxical increase in asthma morbidity and mo
rtality associated with the chronic use of scheduled dosing of short-acting
beta-adrenergic agonists.