Leptin's Role in Multiple Sclerosis

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Leptin's Role in Multiple Sclerosis

By Proceedings of the National Academy of Sciences

Mar 30, 2005, 06:45

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,

relapsing–remitting 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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