beta2-adrenergic receptor stimulation-induced immunosuppressive effects possibly through down-regulation of co-stimulatory molecules, ICAM-1, CD40 and CD14 on monocytes.
We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on the expression of co-stimulatory molecules on lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells. The study found that beta2-AR agonists inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), CD40 and CD14 on monocytes, and that AR agonist activity was antagonized by the selective beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a similar co-stimulatory molecule expression pattern. The LPS-induced production of tumour necrosis factor-alpha was inhibited by AR agonists, and this was also antagonized by butoxamine, and mimicked by salbutamol and terbutaline. The AR agonists also inhibited T-cell proliferation through beta2-AR stimulation. This study clearly demonstrated that endogenous catecholamines elicited immunosuppressive effects through beta2-AR stimulation, possibly due to down-regulation of the expression of ICAM-1, CD40 and CD14 on monocytes. These results suggested that the sympathetic nervous system might regulate the T-helper cell balance via the peripheral end-effectors of the stress system.
Kuroki
K
K
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Takahashi
H K
HK
Iwagaki
H
H
Murakami
T
T
Kuinose
M
M
Hamanaka
S
S
Minami
K
K
Nishibori
M
M
Tanaka
N
N
Tanemoto
K
K
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000420:Albuterol / Q000494:pharmacology; D002078:Butoxamine / Q000494:pharmacology; D019013:CD40 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D007108:Immune Tolerance; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D013726:Terbutaline / Q000494:pharmacology; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D019013:CD40 Antigens; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D018343:Receptors, Adrenergic, beta-2; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D002078:Butoxamine; D018799:Intercellular Adhesion Molecule-1; D013726:Terbutaline; D000420:Albuterol