Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: Increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function

Adipocytes produce the inflammatory cytokine interleukin-6 (IL-6); however, it is not known whether these cells express the IL-6 receptor system, how the secretion of this cytokine is regulated, and whether it has a function within adipose tissue. Using cultured human breast adipocytes, we investiga ted the expression of IL-6 and its receptor system, the effects of IL-6 on main adipocyte functions, and the regulation of IL-6 secretion by catechola mines and glucocorticoids. In the culture system, immunohistochemistry demo nstrated expression of IL-6 and its receptor system, consisting of the liga nd-binding IL-6 receptor and the signal-transducing protein gp130, in matur e adipocytes, but not in undifferentiated adipocyte precursor cells. In fre shly isolated adipocytes, RT-PCR detected messenger ribonucleic acids encod ing the above proteins. Chronic incubation of adipocytes with 1 nmol/L IL-6 during adipose differentiation reduced glycero-3-phosphate dehydrogenase ( GPDH) activity, a marker of adipocyte differentiation, and triglyceride syn thesis to 67 +/- 9% of the basal level (mean +/- SEM; P < 0.05) only on day 21. Incubation of differentiated adipocytes with 10 nmol/L IL-6 for 24 h a lso resulted in a reduction of GPDH activity to 81 +/- 5% (P < 0.05). On th e other hand, 24-h exposure to 10 nmol/L IL-6 increased basal glycerol rele ase by 42 +/- 12% (P < 0.01) and isoproterenol-induced glycerol release by 21 +/- 6% (P < 0.05). The same concentration of IL-6, however, did not alte r basal or insulin-stimulated glucose transport. IL-6 secretion was acutely and chronically stimulated by 1 mu mol/L isoproterenol (peak of 6.2-fold a fter 3 h; P < 0.001) and only moderately suppressed by 100 nmol/L cortisol (-36 +/- 10%; P < 0.001). In conclusion, human breast adipocytes release su bstantial amounts of IL-6 and express IL-6 receptor and gp130. The secretio n of IL-6 by adipocytes is strongly stimulated by beta -adrenergic activati on and is modestly suppressed by glucocorticoids. IL-6 reduces GPDH activit y and stimulates lipolysis, suggesting an autocrine/paracrine role of this cytokine in human adipose breast tissue.