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

Esfandiari, E., McInnes, I. , Lindop, G., Huang, F., Field, M., Komai-Koma, M., Wei, X. and Liew, F. (2001) A proinflammatory role of IL-18 in the development of spontaneous autoimmune disease. Journal of Immunology, 167, pp. 5338-5347. (doi: 10.4049/jimmunol.167.9.5338) (PMID:11673550)

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: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liew, Prof Foo and McInnes, Professor Iain and Komai-Koma, Dr Mousa and Field, Dr Max
• Authors: Esfandiari, E., McInnes, I., Lindop, G., Huang, F., Field, M., Komai-Koma, M., Wei, X., and Liew, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
• Journal Name: Journal of Immunology