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Published Online: 15 July 2005

Beta2-Adrenergic Receptors Mediate the Differential Effects of Catecholamines on Cytokine Production of PBMC

Publication: Journal of Interferon & Cytokine Research
Volume 25, Issue Number 7

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 of β2R 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.

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cover image Journal of Interferon & Cytokine Research
Journal of Interferon & Cytokine Research
Volume 25Issue Number 7July 2005
Pages: 384 - 394
PubMed: 16022583

History

Published online: 15 July 2005
Published in print: July 2005

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Dr. M. Wahle
Department of Medicine IV, University Hospital Leipzig, 04103 Leipzig, Germany.
R.P. Neumann
University Children's Hospital, 23538 Lübeck, Germany.
F. Moritz
Department of Medicine IV, University Hospital Leipzig, 04103 Leipzig, Germany.
A. Krause
Immanuel Hospital, Rheumatology Clinic, 14109 Berlin, Germany.
F. Buttgereit
Department of Medicine, Rheumatology and Clinical Immunology, Charité University Hospital, 10222 Berlin, Germany.
C.G.O. Baerwald
Department of Medicine IV, University Hospital Leipzig, 04103 Leipzig, Germany.

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