beta-Adrenergic regulation of proinflammatory cytokines in humans

Objectives: To investigate the effects of beta-adrenergic stimulation on IL -6 secretion in humans, and to determine the potential contribution to this response of adipocytes and peripheral blood cells (PBC). Design: Experimental study in 8 human volunteers, and in vitro studies on m urine adipocyte cell-line, 3T3.L1 and 3T3.F442A, and human PBC. Measurements: Plasma IL-6 and TNF alpha responses to isoprenaline infusion. Cytokine secretion from differentiated adipocyte cell-lines and PBC in res ponse to isoprenaline. Results: Plasma IL-6 levels increased ninefold (median) by 180 min (baselin e median 0.51 [interquartile range 0.47 - 1.4] vs 180 mins 4.53 [2.58-5.69] pg ml(-1), P = 0.01), One hour after infusion, IL-6 levels (2.9 [1.27 - 3. 98]) were lower than at 180 min (P = 0.05), but higher than baseline (P = 0 .01), TNF alpha levels were unchanged. Differentiated adipocytes incubated in isoprenaline (0-0.1 mu M) released significantly increased amounts of IL -6 whereas no response was elicited from PBC. Conclusions: The induction of IL-6 observed in vivo may be attributed to th e beta-adrenergic stimulation of IL-6 release specifically from adipocytes, as opposed to circulating blood cells.