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

TY - JOUR

T1 - Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males

AU - Matarese, G

AU - Sanna, V

AU - Di Giacomo, A

AU - Lord, G M

AU - Howard, J K

AU - Bloom, S R

AU - Lechler, R I

AU - Fontana, S

AU - Zappacosta, S

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

U2 - 10.1002/1521-4141(200105)31:5<1324::AID-IMMU1324>3.0.CO;2-Y

DO - 10.1002/1521-4141(200105)31:5<1324::AID-IMMU1324>3.0.CO;2-Y

M3 - Article

VL - 31

SP - 1324

EP - 1332

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 5

ER -