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.
Wahle
M
M
Department of Medicine IV, University Hospital Leipzig, 04103 Leipzig, Germany. Matthias.Wahle@medizin.uni-leipzig.de
Neumann
R P
RP
Moritz
F
F
Krause
A
A
Buttgereit
F
F
Baerwald
C G O
CG
D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D009638:Norepinephrine / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine