| First Author | Siegmund B | Year | 2002 |
| Journal | Gastroenterology | Volume | 122 |
| Issue | 7 | Pages | 2011-25 |
| PubMed ID | 12055606 | Mgi Jnum | J:109852 |
| Mgi Id | MGI:3630028 | Doi | 10.1053/gast.2002.33631 |
| Citation | Siegmund B, et al. (2002) Leptin: a pivotal mediator of intestinal inflammation in mice. Gastroenterology 122(7):2011-25 |
| abstractText | BACKGROUND & AIMS: In addition to acting as a regulator of food intake and energy expenditure, leptin can also modulate immune and inflammatory responses. The role of leptin in intestinal inflammation is the focus of the present study. METHODS: Acute and chronic colitis were induced in leptin-deficient ob/ob or wild-type (WT) mice using dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS). The severity of colitis was evaluated, and possible mechanisms were studied. RESULTS: Leptin directly stimulates intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs). In the DSS acute model, ob/ob mice exhibited a 72% reduction of colitis severity and spontaneous release of proinflammatory cytokines from the colon compared with WT mice. Replacement of leptin in ob/ob mice converted disease resistance to susceptibility, indicating that leptin deficiency, not obesity, accounts for the resistance to acute DSS-induced colitis. During chronic DSS-induced colitis and TNBS-induced colitis, in addition to reduced disease severity, ob/ob mice exhibited a significant attenuation in intestinal inflammation, accompanied by reduced production of cytokines and chemokines. When compared with WT mice, CD8(+) IELs of ob/ob mice were reduced in number as well as in their ability to synthesize interferon gamma. In addition, LPMCs of ob/ob mice showed increased apoptosis in untreated as well as DSS- or TNBS-treated mice. Phosphorylation of signal transducer and activator of transcription 3 and induction of cyclooxygenase 2 were absent in the colon of DSS-fed ob/ob mice. CONCLUSIONS: These results show that leptin represents a functional link between the endocrine and immune systems. |
