Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males.
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.
Matarese
G
G
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Italy.
Sanna
V
V
Di Giacomo
A
A
Lord
G M
GM
Howard
J K
JK
Bloom
S R
SR
Lechler
R I
RI
Fontana
S
S
Zappacosta
S
S
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D015994:Incidence; D007371:Interferon-gamma / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000737:chemistry / Q000276:immunology; D012727:Sex Characteristics; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D015431:Weight Loss / Q000187:drug effects
D020738:Leptin; D018991:Myelin Proteolipid Protein; D007371:Interferon-gamma