beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies

J Clin Endocrinol Metab. 2001 Dec;86(12):5864-9. doi: 10.1210/jcem.86.12.8104.


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.

In vitro studies: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipose Tissue / metabolism*
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Adult
  • Animals
  • Clenbuterol / pharmacology
  • Dioxoles / pharmacology
  • Dobutamine / pharmacology
  • Female
  • Humans
  • In Vitro Techniques
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism*
  • Isoproterenol / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Norepinephrine / pharmacology
  • Receptors, Adrenergic, beta / physiology*


  • Adrenergic alpha-Agonists
  • Adrenergic beta-Agonists
  • Dioxoles
  • Interleukin-6
  • Receptors, Adrenergic, beta
  • disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
  • Dobutamine
  • Isoproterenol
  • Norepinephrine
  • Clenbuterol