Leptin Accelerates Autoimmune Diabetes in Female NOD Mice
- Giuseppe Matarese1,
- Veronica Sanna2,
- Robert I. Lechler3,
- Nora Sarvetnick4,
- Silvia Fontana2,
- Serafino Zappacosta1 and
- Antonio La Cava4
- 1Cattedra di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli “Federico II,” Napoli, Italy
- 2Centro di Endocrinologia e Oncologia Sperimentale del CNR, Napoli, Italy
- 3Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.
- 4Department of Immunology, the Scripps Research Institute, La Jolla, California
Abstract
We have recently shown that leptin, the product of the obese gene, can directly influence T-cell function. In the work presented here, we explored the role of leptin in the development of spontaneous autoimmunity in the nonobese diabetic (NOD) mouse, an animal model for the study of human insulin-dependent diabetes mellitus (type 1 diabetes). We found that expression of serum leptin increased soon before the onset of hyperglycemia and diabetes in susceptible females. A pathogenetic role of leptin was assessed by administering recombinant leptin to young female and male NOD mice. Intraperitoneal injections of leptin accelerated autoimmune destruction of insulin-producing β-cells and significantly increased interferon-γ production in peripheral T-cells. These findings indicate that leptin can favor proinflammatory cell responses and directly influence development of autoimmune disease mediated by Th1 responses.
Footnotes
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Address correspondence and reprint requests to Serafino Zappacosta, Cattedra di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli “Federico II,” Via S. Pansini 5, 80131, Napoli, Italy. E-mail: zappacos{at}unina.it; or to Antonio La Cava, Department of Medicine, University of California Los Angeles, 1000 Veteran Avenue, Rehabilitation Center 32-59, Los Angeles, CA. E-mail: ALaCava{at}mednet.ucla.edu.
Received for publication 31 May 2001 and accepted in revised form 28 January 2002.
Ab, antibody; Ag, antigen; BG, blood glucose; ELISA, enzyme-linked immunosorbent assay; IFN-γ, interferon-γ; IL, interleukin; i.p., intraperitoneal; TNF-α, tumor necrosis factor-α.
- DIABETES
