Leptin accelerates autoimmune diabetes in female NOD mice.
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 beta-cells and significantly increased interferon-gamma 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.
Matarese
Giuseppe
G
Cattedra di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli "Federico II," Napoli, Italy.
Sanna
Veronica
V
Lechler
Robert I
RI
Sarvetnick
Nora
N
Fontana
Silvia
S
Zappacosta
Serafino
S
La Cava
Antonio
A
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000276:immunology* / Q000401:mortality; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics; D020738:Leptin / Q000097:blood* / Q000494:pharmacology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology
D020738:Leptin; D012333:RNA, Messenger; D007371:Interferon-gamma