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

J Interferon Cytokine Res. 2005 Jul;25(7):384-94. doi: 10.1089/jir.2005.25.384.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic AMP / biosynthesis
  • Cytokines / biosynthesis*
  • Epinephrine / pharmacology*
  • Humans
  • Leukocytes, Mononuclear / chemistry
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology*
  • Lymphocyte Activation
  • Norepinephrine / pharmacology*
  • Receptors, Adrenergic, beta-2 / analysis
  • Receptors, Adrenergic, beta-2 / physiology*
  • T-Lymphocytes / immunology


  • Cytokines
  • Receptors, Adrenergic, beta-2
  • Cyclic AMP
  • Norepinephrine
  • Epinephrine