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Leptin's Role in Multiple Sclerosis
By Proceedings of the National Academy of Sciences,
Mar 30, 2005 - 6:44:38 AM
According to Giuseppe Matarese et al., increased levels of the cytokine-like hormone leptin in individuals with multiple sclerosis (MS) inversely correlates with the frequency of CD4+CD25+ regulatory T cells (TRegs).
Previous research has shown that leptin plays a significant role in the pathogenesis of autoimmune diseases such as experimental autoimmune encephalomyelitis, an animal model for MS.
The role of leptin in the pathogenesis of human MS is not fully understood. The authors studied 126 naïve-to-therapy, relapsingremitting MS patients and detected an increase in leptin in both their cerebrospinal fluid and serum.
This increase correlated with elevated IFN-γ levels. Matarese et al. generated T cell lines from three of the individuals and, after activating the cells with human myelin basic protein, found an increase in leptin production and up-regulation of the leptin receptor.
Antileptin or an antileptin receptor blocking antibody inhibited the proliferative response of these T cells by up to 60%. Immunophenotypic analysis of peripheral blood from the MS patients showed a significant reduction in percentage and absolute number of TRegs, whereas no difference was observed in the frequency of other cell subpopulations. Treatment of experimental autoimmune encephalomyelitis mice with leptin antagonists increased the percentage of TRegs and slowed disease progression.
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