β-Adrenergic Regulation of IL-6 Release from Adipose Tissue:In Vivoandin VitroStudies

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 β-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 (β1 agonist), clenbuterol (β2), CL316243 (β3), 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 β2/β3 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.