Beta2-adrenergic receptors mediate the differential effects of catecholamines on cytokine production of PBMC.

We determined characteristics of beta2-adrenergic receptors (beta2R) on peripheral blood mononuclear cells (PBMC) and cytokine production after mitogenic stimulation and coincubation with catecholamines. PBMCs were stimulated with interleukin-2 (IL-2), tetanus toxoid (TT), anti-CD3 antibody, or phytohemagglutinin (PHA). The cytokines interferon-gamma (IFN-gamma), IL-4, and IL-6 were determined by ELISA following coincubation with high-dose (10(-5) M) and low-dose (10(-9) M) epinephrine (EPI) and norepinephrine (NE). Intracellular IFN-gamma and IL-4 were studied by FACS analysis. The beta2R density was investigated using a radioligand binding assay. The stimuli induced various cytokine profiles in PBMCs. Synthesis of IFN-gamma was induced by all mitogens and could be suppressed by catecholamines (26%-85% reduction). In PHA-stimulated PBMCs, IL-4 synthesis was decreased by high-dose catecholamines (24%-28% reduction). Adding a beta-blocking agent attenuated most catecholamine effects. A highly significant negative correlation between the density of beta2R with IFN-gamma and IL-6 levels of PHA-activated PBMCs (r = -0.88 to -0.96, p < 0.01-< 0.001) was observed. The results indicate that the density of beta2R on PBMC plays a role in mediating the differential catecholamine effects on cytokine production of PBMC. Furthermore, changes in cytokine expression induced by catecholamines favor Th2 responses.