Restricted leptin antagonism as a therapeutic approach to treatment of autoimmune diseases.

Leptin, the adipocyte derived hormone, has a pivotal role in regulating energy homeostasis and appetite. Beyond this essential role in bodyweight control, leptin also regulates the immune responses. Leptin has pro-inflammatory effects on T cell populations, shifting the T helper balance towards a TH1 phenotype, through induction of pro-inflammatory cytokines and stimulation of macrophage and natural killer cell function. Acute starvation reduces serum leptin levels, resulting in an impaired cellular immune response. The TH1 pro-inflammatory immune response, a homeostatic response mediated by the low leptin levels, is also impaired during starvation. Leptin-deficient or leptin receptor mutant mice are protected against the development of several inflammatory or various T cell-dependent autoimmune diseases. Therefore, leptin appears to have a central role in the immune response and low leptin levels may protect against autoimmune disease. Here we review the role of leptin in the immune responses, with emphasis on autoimmune diseases. We will also discuss the application of leptin antagonist therapy for prevention and treatment of immunity related disorders.