beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies.
Circulating IL-6 levels are elevated in obesity. Although IL-6 is expressed in adipose tissue, neither its regulation nor cell of origin is well characterized. Here we investigated the beta-adrenergic regulation of IL-6 release in a combination of studies on humans and animals in vivo and cultured adipocytes in vitro. Human in vivo study: Human volunteers were infused with isoproterenol, norepinephrine, or saline [4 M:4F; mean (SD) age 35.5 (5.8) yr; body mass index 24.6 (4.2) kg/m(-2)]. Plasma IL-6 levels increased during a 3-h infusion of isoproterenol (P = 0.01) and fell 2 h post infusion (P = 0.05). IL-6 levels did not change significantly with either norepinephrine or saline. Murine in vivo study: C57BL6/J male mice were injected ip with dobutamine (beta(1) agonist), clenbuterol (beta(2)), CL316243 (beta(3)), or saline placebo. Plasma IL-6 levels at 3 h were increased by clenbuterol (P = 0.02) and CL316243 (P = 0.02) but not dobutamine (P = 0.51), compared with placebo.


METHODS
In human peripheral blood cells, lipopolysaccharide treatment enhanced secretion of IL-6 (vs. controls; P < 0.001), whereas isoproterenol inhibited IL-6 secretion (P = 0.012) and norepinephrine had no significant effect. In contrast, isolated human adipocytes and differentiated 3T3F442A adipocytes all rapidly secreted IL-6 in response to adrenergic agonists (P < 0.01, compared with untreated cells). We conclude that beta 2/beta 3 adrenoceptor stimulation on adipocytes, rather than macrophages, may be responsible for the increases in plasma IL-6 concentrations observed during sympathetic activation and in obesity.
Mohamed-Ali
V
V
Department of Medicine, University College London Medical School, Whittington Hospital, London N19 3UA, United Kingdom.
Flower
L
L
Sethi
J
J
Hotamisligil
G
G
Gray
R
R
Humphries
S E
SE
York
D A
DA
Pinkney
J
J
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000818:Animals; D002976:Clenbuterol / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002976:Clenbuterol; D004149:Dioxoles; D004280:Dobutamine; D015850:Interleukin-6; D007545:Isoproterenol; D009638:Norepinephrine; D011943:Receptors, Adrenergic, beta; D000093242:Interleukin-6 Inhibitors; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate