ABSTRACT
Leptin has been implicated as a pro-inflammatory cytokine, involved in the activation o f effector T-cells as well as various other components o f the innate and adaptive immune response. Leptin-deficient ob/ob mice exhibit resistance to several T-cell-mediated autoim mune disorders including experimental arthritis, hepatitis and experimental allergic encephalomy elitis. Inhibition o f the leptin-induced pro-immune response may be useful as a therapeutic tool in T-cell-mediated autoimmune disorder. Herein, we report on the use o f our recently developed competitive leptin antagonist as an anti-inflammatory agent in models o f acute and chronic T-cell-mediated liver inflammation and chronic liver fibrosis. This beneficial effect may be medi ated by both direct T-cell modulatory effects and inhibition o f hepatic stellate cell activation and function, leading to alleviation o f liver fibrosis. O ur results suggest that leptin inhibition may be developed into a rational imm unomodulatory therapeutic modality.
