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Ehsanollah Esfandiari, Iain B McInnes, George Lindop, Fang-Ping Huang, Max Field, Mousa Komai-Koma, Xiao-qing Wei, Foo Y Liew, A Proinflammatory Role of IL-18 in the Development of Spontaneous Autoimmune Disease, The Journal of Immunology, Volume 167, Issue 9, November 2001, Pages 5338–5347, https://doi.org/10.4049/jimmunol.167.9.5338
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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.