Open AccessA Proinflammatory Role of IL-18 in the Development of Spontaneous Autoimmune Disease
Author(s) -
Ehsanollah Esfandiari,
Iain B. McInnes,
George B.M. Lindop,
Fang-Ping Huang,
Max Field,
Mousa KomaiKoma,
XiaoQing Wei,
Foo Y. Liew
Publication year - 2001
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.167.9.5338
Subject(s) - proinflammatory cytokine , medicine , immunology , rash , autoimmune disease , inflammation , systemic lupus erythematosus , autoimmunity , systemic disease , disease , immune system , immunopathology , antibody
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.
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