Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue

IL-8 is released from human adipose tissue. Circulating IL-8 is increased in obese compared with lean subjects and is associated with measures of insulin resistance, development of atherosclerosis, and cardiovascular disease. We studied 1) the production and release of IL-8 in vitro from paired samples of subcutaneous ( SAT) and visceral ( VAT) adipose tissue and 2) the production of IL-8 from whole adipose tissue, isolated adipocytes, and nonfat cells of adipose tissue. IL-8 release from VAT was fourfold higher than from SAT ( P < 0.05), and IL-8 mRNA was twofold higher in VAT compared with SAT (P < 0.01). Dexamethasone ( 50 nM) attenuated IL-8 production by 50% (P < 0.05), and IL-1β (2 μg/l) increased IL-8 production up to 15-fold ( P < 0.001). IL- 8 release from whole SAT explants correlated with body mass index (BMI; r = 0.78; P < 0.001), as did IL-8 release from nonfat cells (r = 0.79; P < 0.001). However, no correlation was found between IL-8 release from the fraction of isolated adipocytes and BMI ( r = 0.01). In conclusion, we demonstrated an increased release of IL- 8 from VAT compared with SAT. Furthermore, our data suggest that the observed elevation in circulating levels of IL- 8 in obese subjects is due primarily to the release of IL- 8 from nonfat cells from adipose tissue. The high levels of IL- 8 release from human adipose tissue and accumulation of this tissue in obese subjects may account for some of the increase in circulating IL- 8 observed in obesity.