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

1 Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital and Faculty of Health Sciences, Aarhus University, DK-8000 Aarhus C; 2 Department of Gynecology and Obstetrics, Skejby Sygehus, Aarhus University Hospital, DK-8200 Aarhus N, Denmark; and Departments of 3 Surgery and 4 Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163 Submitted 17 June 2003 ; accepted in final form 10 September 2003 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-1 (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. interleukin-8; interleukin-6; human; obesity; atherosclerosis Address for reprint requests and other correspondence: J. M. Bruun, Dept. of Endocrinology and Metabolism, Aarhus Amtssygehus, Tage Hansensgade 2, DK-8000 Aarhus C, Denmark (E-mail: Jens.Bruun{at}iekf.au.dk ).