title: Leptin-deficient mice are protected from accelerated nephrotoxic nephritis.
abstract: Leptin is an adipose tissue-derived hormone that signals nutritional status to the hypothalamus. Recent evidence indicates that leptin modifies proinflammatory immune responses and may provide a key link between nutritional deficiency and immune dysfunction. To study the influence of leptin deficiency on immune-mediated renal disease, susceptibility to accelerated nephrotoxic nephritis was examined in leptin-deficient C57BL/6-ob/ob mice and C57BL/6 wild-type controls. The model was induced with sheep anti-mouse glomerular basement membrane antibody injected to mice preimmunized against sheep IgG, and mice were sacrificed 8 days after induction of disease. The leptin-deficient ob/ob mice were strongly protected from glomerular crescent formation, macrophage infiltration, glomerular thrombosis, and albuminuria in this model. Our findings suggest that leptin is required for the induction and maintenance of immune-mediated glomerulonephritis, and that blockade of the leptin axis might provide an attractive therapeutic possibility in human autoimmune disease.
authors.affiliation: Department of Renal Medicine and Transplantation, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Tarzi
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Ian
authors.initials: I
authors.lastname: Jackson
authors.forename: Charles D
authors.initials: CD
authors.lastname: Pusey
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D004198:Disease Susceptibility; D005455:Fluorescent Antibody Technique; D005916:Globulins / Q000633:toxicity; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007678:Kidney Glomerulus / Q000473:pathology; D020738:Leptin / Q000097:blood / Q000172:deficiency*; D008297:Male; D051379:Mice; D009393:Nephritis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology
chemical_list: D005916:Globulins; D007074:Immunoglobulin G; D020738:Leptin