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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 2 783-791
Copyright © 2001 by The Endocrine Society

Original Studies

Leptin Directly Induces the Secretion of Interleukin 1 Receptor Antagonist in Human Monocytes1

Cem Gabay2, Magali G. Dreyer2, Nathalie Pellegrinelli, Rachel Chicheportiche and Christoph A. Meier

Department of Internal Medicine, Division of Rheumatology (C.G., N.P.), Division of Endocrinology and Diabetes (M.G.D., C.A.M.), and Division of Immunology and Allergy (R.C.), University Hospital Geneva, CH-1211 Geneva, Switzerland

Address correspondence and requests for reprints to: Dr. Christoph A. Meier, Division of Endocrinology and Diabetes, University Hospital Geneva, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail: cameier{at}bluewin.ch

Besides its actions on the regulation of appetite, leptin has also been implicated in regulating reproductive and immune functions. Because leptin-deficient mice are more susceptible to lipopolysaccharide- and tumor necrosis factor-{alpha}-induced shock, which is associated with lower levels of interleukin 1 receptor antagonist (IL-1Ra), we investigated whether leptin is a direct regulator of IL-1Ra in human monocytes. In human moncytic cells, leptin was capable of inducing a 6- to 10-fold increase in secreted IL-1Ra in a time- and dose-dependent manner. Moreover, leptin induced the messenger RNA for IL-1Ra within 8 h and specifically activated the promoter for this gene. However, leptin had no effect on the expression or secretion of IL-1 in THP-1 cells. This effect of leptin on monocytic cells requires the presence of the functional leptin receptor OB-Rb, which we have shown to be present in human monocytes by RT-PCR and by measuring the activation of the Jak/STAT pathway.

In summary, we have demonstrated that leptin is capable of inducing the expression and secretion of IL-1Ra by human monocytes, an effect that is potentially mediated through the presence of functional leptin receptors on these cells. These findings suggest that leptin may have immunomodulatory functions in vivo.




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