Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males

Eur J Immunol. 2001 May;31(5):1324-32. doi: 10.1002/1521-4141(200105)31:5<1324::AID-IMMU1324>3.0.CO;2-Y.


SJL (H-2s) female mice are more susceptible than males to experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin-derived peptides. The reasons for this sexual dimorphism are unclear, but may include such factors as sex-related differences in immune responsiveness, hormonal effects and sex-linked genetic factors. Recent evidence indicates that leptin modifies T cell immunity promoting T helper (Th) 1 pro-inflammatory immune responses. Circulating leptin levels show a marked sexual dimorphism, being higher in females than in males. In the present study, we investigated whether leptin treatment altered the course of relapsing-remitting EAE, induced by the proteolipid protein peptide (PLP(139-151)), in SJL susceptible females and EAE-resistant males. Administration of leptin to female SJL mice before or after disease onset significantly worsened the disease, with a concomitant increase in the PLP(139-151)-specific delayed-type hypersensitivity (DTH) reactivity and in vitro IFN-gamma secretion. Leptin treatment at priming with antigen or before disease onset rendered male SJL mice susceptible to EAE, with the appearance of PLP(139-151)-specific DTH reactivity and a switch from a Th2 to Th1 pattern of cytokine release. Our findings indicate that leptin administration to susceptible females resulted in a more severe disease, and that reduced leptin levels in male SJL mice may contribute to the gender-related differences in the induction phase of EAE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Central Nervous System / drug effects
  • Central Nervous System / pathology
  • Disease Susceptibility*
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Hypersensitivity, Delayed / immunology
  • Incidence
  • Interferon-gamma / metabolism
  • Leptin / administration & dosage
  • Leptin / pharmacology*
  • Lymph Nodes / immunology
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Myelin Proteolipid Protein / chemistry
  • Myelin Proteolipid Protein / immunology
  • Sex Characteristics*
  • Spleen / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Weight Loss / drug effects


  • Leptin
  • Myelin Proteolipid Protein
  • Interferon-gamma