Journal of Leukocyte Biology
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A more recent version of this article appeared on October 1, 2004 Originally published online as doi:10.1189/jlb.0404239 on July 26, 2004

Published online before print July 7, 2004
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0404239

Received for publication April 16, 2004.
Revised May 27, 2004.
Accepted for publication June 13, 2004.

Article

Development of intestinal inflammation in double IL-10- and leptin-deficient mice

Britta Siegmund *, Joseph A. Sennello {dagger}, Hans A. Lehr; {ddagger}, Arvind Batra *, Inka Fedke *, Martin Zeitz *, and Giamila Fantuzzi {dagger}@

*Charité Universitaetsmedizin Berlin, Campus Benjamin Franklin, Germany; {dagger}Department of Medicine, University of Colorado Health Sciences Center, Denver; and {ddagger}Institute of Pathology, University of Mainz, Germany


  Abstract

Leptin-deficient (ob/ob) mice are resistant in different models of autoimmunity and inflammation, suggesting that leptin regulates immunity and inflammation. To investigate whether leptin deficiency modulates the spontaneous intestinal inflammation observed in interleukin (IL)-10-deficient mice, double IL-10- and leptin-deficient [IL-10 knockout (KO) ob/ob] mice were generated and compared with single IL-10 KO mice for colitis severity. Body weight in IL-10 KO ob/ob mice was significantly reduced compared with that of ob/ob mice. However, when compared with wild-type or IL-10 KO mice, IL-10 KO ob/ob mice were still markedly obese. IL-10 KO and IL-10 KO ob/ob mice developed colitis with a comparable time-course and severity in terms of macroscopic and histologic scores. Likewise, production of interferon-{gamma}, IL-6, and IL-13 from colon cultures and splenocytes did not differ among these two groups. Conversely, rates of apoptosis were higher in lamina propria lymphocytes obtained from the colon of IL-10 KO ob/ob compared with IL-10 KO mice. In conclusion, although leptin deficiency has been associated with resistance in models of autoimmunity and inflammation induced by exogenous stimuli, leptin appears not to play a significant role in the spontaneous colitis of IL-10 KO mice, although it modulates survival of intestinal lymphocytes.

Key Words: obesity • cytokines • colon • leptin






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Copyright © 2004 by the Society for Leukocyte Biology.