A role for leptin in immune-mediated inflammatory diseases?

Excerpt

Leptin, the product of the Ob gene, is a polypeptide hormone that plays an important role in the regulation of body weight by inhibiting food intake and stimulating energy expenditure. Moreover, leptin exhibits a variety of other effects including the regulation of endocrine function, reproduction and hematopoiesis. Consistently, leptin-deficient mice are not only obese, but display major hormonal disturbances, including hypercorticosteronemia, diabetes, and infertility. In addition, it has been known for many years that leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice have an altered immune response. More recent studies have shown that T cells and B cells express the long signaling leptin receptor isoform (ObRb) and that leptin exerts direct effects on T lymphocytes, including the stimulation of cell proliferation, the promotion of Th1 responses, and the protection of thymocytes from corticosteroid-induced apoptosis. Consistently, ob/ob mice are protected from inflammation mediated by T cells and B cells in some models such as experimental colitis, experimental autoimmune encephalomyelitis, and concanavalin A-induced hepatitis. Conversely, the administration of recombinant leptin increased the severity of experimental autoimmune encephalomyelitis. Using a model of antigen-induced arthritis, we demonstrated that ob/ob and db/db mice have a milder form of arthritis and that cellular and humoral immune responses to the injected antigen are decreased as compared with wild-type mice. Furthermore, ex vivo stimulated lymph node cells from ob/ob and db/db mice produced less interferon gamma and more IL-10 than cells obtained from control mice. …