Beta 2 -Adrenergic Receptors Mediate the Differential Effects of Catecholamines on Cytokine Production of PBMC

Abstract

We determined characteristics of β₂-adrenergic receptors (β2R) 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-γ (IFN-γ), 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-γ and IL-4 were studied by FACS analysis. The β2R density was investigated using a radioligand binding assay. The stimuli induced various cytokine profiles in PBMCs. Synthesis of IFN-γ 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 ofβ2R with IFN-γ 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 β2R 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.