A proinflammatory role of IL-18 in the development of spontaneous autoimmune disease

Esfandiari, Ehsanollah, McInnes, Iain B., Lindop, George, Huang, Fang Ping, Field, Max, Komai-Koma, Mousa, Wei, Xiao-Qing ORCID: https://orcid.org/0000-0002-6274-8503 and Liew, Foo Yew 2001. A proinflammatory role of IL-18 in the development of spontaneous autoimmune disease. The Journal of Immunology 167 (9) , pp. 5338-5347.

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Last Modified:	21 Oct 2022 09:14
URI:	https://orca.cardiff.ac.uk/id/eprint/35682

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