Norepinephrine modulates human dendritic cell activation by altering cytokine release.
Norepinephrine (NE) can modulate dendritic cell (DC) activation in animal models, but the response of human DC to NE and other response modifiers is as yet not completely understood. Here we report the effect of NE on the cytokine response of a mixed population of human DC cells to extracellular stimuli. These cells were obtained by differentiating human cord blood CD34+ precursor cells. NE inhibited the lipopolysaccharide (LPS)-stimulated production of interleukin (IL)-23, IL-12 p40, tumor necrosis factor (TNF)-alpha and IL-6 whereas the expression of IL-10 was not significantly affected. Thus, human cord blood-derived DC respond to NE in a manner similar to mouse Langerhans cells (LC). Furthermore, forskolin also inhibited the LPS-induced levels of TNF-alpha, IL-12 p40, IL-23 p19 and IL-6, supporting the hypothesis that the effects of NE are mediated by cAMP. Data from experiments using inhibitors of adrenergic receptors suggest that NE acts through beta-adrenergic receptors. As IL-23 promotes the differentiation of CD4+ T cells required for T(H)1-mediated immunity, we suggest that NE decreases the differentiation of CD4+ T cells needed for T(H)1-mediated contact hypersensitivity and that NE is a candidate regulator of human DC functions in the skin.
Goyarts
Earl
E
Clinique Laboratories, Melville, NY 11747, USA. egoyarts@estee.com
Matsui
Mary
M
Mammone
Tom
T
Bender
Anna M
AM
Wagner
John A
JA
Maes
Daniel
D
Granstein
Richard D
RD
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009638:Norepinephrine / Q000276:immunology / Q000494:pharmacology*; D013566:Sympathomimetics / Q000276:immunology / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018952:Antigens, CD34; D007378:Interleukins; D008070:Lipopolysaccharides; D013566:Sympathomimetics; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D009638:Norepinephrine