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High-Dose Leptin Activates Human Leukocytes Via Receptor Expression on Monocytes

Zarkesh-Esfahani, H., Pockley, A.G., Metcalfe, R.A., Bidlingmaier, M., Wu, Z., Ajami, A., Weetman, A.P., Strasburger, C.J. and Ross, R.J.M. (2001) High-Dose Leptin Activates Human Leukocytes Via Receptor Expression on Monocytes. Journal of Immunology, 167 (8). pp. 4593-4599. ISSN 1550-6606

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Leptin is capable of modulating the immune response. Proinflammatory cytokines induce leptin production, and we now demonstrate that leptin can directly activate the inflammatory response. RNA expression for the leptin receptor (Ob-R) was detectable in human PBMCs. Ob-R expression was examined at the protein level by whole blood flow cytometry using an anti-human Ob-R mAb 9F8. The percentage of cells expressing leptin receptor was 25 ± 5% for monocytes, 12 ± 4% for neutrophils, and 5 ± 1% for lymphocytes (only B lymphocytes). Incubation of resting PBMCs with leptin induced rapid expression of TNF-α and IL-6 mRNA and a dose-dependent production of TNF-α and IL-6 by monocytes. Incubation of resting PBMCs with high-dose leptin (250 ng/ml, 3–5 days) induced proliferation of resting cultured PBMCs and their secretion of TNF-α (5-fold), IL-6 (19-fold), and IFN-γ (2.5-fold), but had no effect on IL-4 secretion. The effect of leptin was distinct from, and additive to, that seen after exposure to endotoxin or activation by the mixed lymphocyte reaction. In conclusion, Ob-R is expressed on human circulating leukocytes, predominantly on monocytes. At high doses, leptin induces proinflammatory cytokine production by resting human PBMCs and augments the release of these cytokines from activated PBMCs in a pattern compatible with the induction of Th1 cytokines. These results demonstrate that leptin has a direct effect on the generation of an inflammatory response. This is of relevance when considering leptin therapy and may partly explain the relationship among leptin, proinflammatory cytokines, insulin resistance, and obesity.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2001 by The American Association of Immunologists, Inc.
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Clinical Sciences Division North (Sheffield)
Depositing User: Repository Officer
Date Deposited: 15 Aug 2005
Last Modified: 08 Feb 2013 16:47
Published Version: http://www.jimmunol.org/cgi/content/full/167/8/459...
Status: Published
Refereed: Yes
URI: http://eprints.whiterose.ac.uk/id/eprint/584

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