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Human Breast Adipocytes Express Interleukin-6 (IL-6) and Its Receptor System: Increased IL-6 Production by ß-Adrenergic Activation and Effects of IL-6 on Adipocyte Function

German Diabetes Research Institute, 40225 Dusseldorf, Germany; and Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health (S.R.B., G.P.C.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Hans Hauner, M.D., German Diabetes Research Institute, Auf’m Hennekamp 65, 40225 Dusseldorf, Germany. E-mail: hauner{at}dfi.uni-duesseldorf.de

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 investigated 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 catecholamines and glucocorticoids. In the culture system, immunohistochemistry demonstrated expression of IL-6 and its receptor system, consisting of the ligand-binding IL-6 receptor and the signal-transducing protein gp130, in mature adipocytes, but not in undifferentiated adipocyte precursor cells. In freshly isolated adipocytes, RT-PCR detected messenger ribonucleic acids encoding 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 synthesis 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 also resulted in a reduction of GPDH activity to 81 ± 5% (P < 0.05). On the other hand, 24-h exposure to 10 nmol/L IL-6 increased basal glycerol release 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 alter basal or insulin-stimulated glucose transport. IL-6 secretion was acutely and chronically stimulated by 1 µmol/L isoproterenol (peak of 6.2-fold after 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 substantial amounts of IL-6 and express IL-6 receptor and gp130. The secretion of IL-6 by adipocytes is strongly stimulated by ß-adrenergic activation and is modestly suppressed by glucocorticoids. IL-6 reduces GPDH activity and stimulates lipolysis, suggesting an autocrine/paracrine role of this cytokine in human adipose breast tissue.

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