Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo.

To investigate in vivo adipose tissue production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and their soluble receptors: TNF receptor type I (sTNFR-I), TNF receptor type II (sTNFR-II), and IL-6 receptor (sIL-6R), we determined arteriovenous differences in their levels across abdominal subcutaneous adipose tissue in obese subjects. Subjects had a median (interquartile range) age of 44.5 (27-51.3) yr, body mass index (BMI) of 32.9 (26.0-46.6) kg/m2, and %body fat of 42.5 (28.5-51.2) %. Although there was not a significant difference in the arteriovenous concentrations of TNF-α ( P = 0.073) or sTNFR-II ( P = 0.18), the levels of sTNFR-I ( P = 0.002) were higher in the vein compared with artery, suggesting adipose tissue production of this soluble receptor. There was a significant arteriovenous difference in IL-6 ( P < 0.001) but not in its soluble receptor ( P = 0.18). There was no relationship between TNF-α levels and adiposity indexes ( r s = 0.12-0.22, P = not significant); however, levels of both its soluble receptor isomers correlated significantly with BMI and %body fat (sTNFR-I r s = 0.42-0.72, P < 0.001; sTNFR-II r s = 0.36-0.65, P < 0.05- <0.001). IL-6 levels correlated significantly with both BMI and %body fat ( r s = 0.51, P = 0.004, and r s = 0.63, P < 0.001), but sIL-6R did not. In conclusion, 1) soluble TNFR-I is produced by adipose tissue, and concentrations of both soluble isoforms correlate with the degree of adiposity, and 2) IL-6, but not its soluble receptor, is produced by adipose tissue and relates to adiposity.