title: A proinflammatory role of IL-18 in the development of spontaneous autoimmune disease.
abstract: Serum from patients with systemic lupus erythematosus (SLE) contained significantly higher concentrations of IL-18 than normal individuals. MRL/lpr mice, which develop spontaneous lupus-like autoimmune disease, also had higher serum levels of IL-18 than wild-type MRL/++ mice. Daily injections of IL-18 or IL-18 plus IL-12 resulted in accelerated proteinuria, glomerulonephritis, vasculitis, and raised levels of proinflammatory cytokines in MRL/lpr mice. IL-18-treated MRL/lpr mice also developed a "butterfly" facial rash resembling clinical SLE. In contrast, MRL/lpr mice treated with IL-18 plus IL-12 did not develop a facial rash. The facial lesion in the IL-18-treated mice showed epidermal thickening with intense chronic inflammation accompanied by increased apoptosis, Ig deposition, and early systemic Th2 response compared with control or IL-12 plus IL-18-treated mice. These data therefore show that IL-18 is an important mediator of lupus-like disease and may thus be a novel target for therapeutic intervention of spontaneous autoimmune diseases.
authors.affiliation: Department of Immunology and Bacteriology, Centre of Rheumatic Disease, Glasgow, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Esfandiari
authors.forename: I B
authors.initials: IB
authors.lastname: McInnes
authors.forename: G
authors.initials: G
authors.lastname: Lindop
authors.forename: F P
authors.initials: FP
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Field
authors.forename: M
authors.initials: M
authors.lastname: Komai-Koma
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.forename: F Y
authors.initials: FY
authors.lastname: Liew
mesh_terms: D000328:Adult; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000209:etiology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008875:Middle Aged
chemical_list: D000974:Antibodies, Antinuclear; D016207:Cytokines; D020382:Interleukin-18; D018664:Interleukin-12