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

被引:4
|
作者
Matarese, G
Sanna, V
Di Giacomo, A
Lord, GM
Howard, JK
Bloom, SR
Lechler, RI
Fontana, S
Zappacosta, S
机构
[1] Univ Naples Federico II, Cattedra Immunol, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy
[2] CNR, CEOS, Ctr Endocrinol & Oncol Sperimentale, I-80125 Naples, Italy
[3] Azienda Osped V Monaldi, Lab Immunol Cellulare, Naples, Italy
[4] Univ London Imperial Coll Sci Technol & Med, Sch Med, Hammersmith Hosp, Dept Immunol, London, England
[5] Univ London Imperial Coll Sci Technol & Med, Sch Med, Endocrine Unit, Hammersmith Hosp, London, England
基金
英国医学研究理事会;
关键词
EAE; leptin; autoimmunity; sex hormones; multiple sclerosis;
D O I
10.1002/1521-4141(200105)31:5<1324::AID-IMMU1324>3.0.CO;2-Y
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
SJL (H-2(5)) 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 proinflammatory 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 (PLP139-151), 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 PLP139-151-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 PLP139-151-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.
引用
收藏
页码:1324 / 1332
页数:9
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