The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/1/171/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 1, January 6, 1997 171-176

Brief Definitive Reports

Multiple Cytokines and Acute Inflammation Raise Mouse Leptin Levels: Potential Role in Inflammatory Anorexia

Pasha Sarraf*, Robert C. Frederich{ddagger}, Ewa M. Turner*, Grace Ma*, Nora T. Jaskowiak*, Dennis J. Rivet, III*, Jeffrey S. Flier{ddagger}, Bradford B. Lowell{ddagger}, Douglas L. Fraker*, and H. Richard Alexander*

From * The Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; and {ddagger} Division of Endocrinology, Beth Israel Hospital, Boston, Massachusetts 02215

Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions.

Address correspondence to H. Richard Alexander, Jr., Head, Surgical Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B17, Bethesda, MD 208921502.

The authors wish to thank Michael Nishimura, Rudy Pozzatti, and James Gnarra for their technical advice and support. The assistance of Aida Ordoubadi and Aaron Rosenfeld is gratefully acknowledged. We also wish to thank Dr. Carl Grunfeld for valuable discussions and sharing of data before publication. Finally, we thank Barbara Owen for her help in preparation of the manuscript.


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