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

• Published in: European journal of immunology 2001-05, Vol.31 (5), p.1324-1332
• Main Authors: Matarese, Giuseppe, Sanna, Veronica, Giacomo, Antonio Di, Lord, Graham M., Howard, Jane K., Bloom, Stephen R., Lechler, Robert I., Fontana, Silvia, Zappacosta, Serafino
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Autoimmunity; Cells, Cultured; Central Nervous System - drug effects; Central Nervous System - pathology; Disease Susceptibility; EAE; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; g-Interferon; Hypersensitivity, Delayed - immunology; Incidence; Interferon-gamma - metabolism; Leptin; Leptin - administration & dosage; Leptin - pharmacology; Lymph Nodes - immunology; Lymphocyte Activation - drug effects; Male; Mice; Multiple sclerosis; Myelin Proteolipid Protein - chemistry; Myelin Proteolipid Protein - immunology; Sex Characteristics; Sex hormones; Spleen - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology; Weight Loss - drug effects
• ISSN: 0014-2980; 1521-4141
• 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 (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‐γ 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.