OP0010 Neutralisation of il-18 activity is a disease-modifying therapy in the murine collagen-induced arthritis model. (1st June 2001)

• Record Type: Journal Article
• Authors: Plater-Zyberk, C; Joosten, LA; Helsen, MA; Sattonnet-Roche, P; Siegfried, C; Alouani, S; Van de Loo, AJ; Graber, P; Lubberts, E; Dinarello, CA; Van den Berg, WB; Chvatcko, Y
• Is Part Of: Annals of the rheumatic diseases. Volume 60(2001)Supplement 1
• Page Start: A371
• Page End: A372
• Publication Date: 2001-06-01
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2001.942
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Interleukin-18 (IL-18) is a member of the interleukin-1 cytokine family. In vivo IL-18 has been demonstrated as promoting the development of a TH1 response in synergy with IL-12. Patients with rheumatoid arthritis (RA) have in their joints significant levels of IL-18 and IL-12. Objectives: This study was aimed at studying the effect of neutralising endogenous IL-18 in vivo in collagen-induced arthritic (CIA) mice, to define the therapeutic potentials of IL-18 blockade for the treatment of patients with RA. Methods: Two distinct IL-18 neutralising strategies were used, i.e. a recombinant human IL-18 binding protein (rIL-18BP) and a polyclonal rabbit anti-mouse IL-18 IgG, to treat CIA mice in a therapeutic protocol (after disease onset). The effect on disease severity (visual scores) as well as parameters of cartilage and bone destruction were evaluated. Results: Clinical scores were significantly reduced after IL-18 blockade (rhIL-18BP 1 mg/kg, p < 0.001, n = 13; anti-IL18 IgG, 2 mg, p < 0.05, n = 9, Mann Whitney test, treated versus placebo groups). Histological examination showed cartilage protection (decrease erosion scores, p < 0.05) that was accompanied by significantly reduced levels of serum cartilage oligomeric matrix protein (an indicator of cartilage turnover) and VDIPEN expression (a neoepitope present after digestion by matrix metalloproteinases). X-ray analysis of joints provided evidence of reduced bone erosion. Conclusion: These results clearly demonstrate that neutralising endogenous IL-18 is therapeutically efficacious in the CIA model and support the use of IL-18 neutralisation as a novel cartilage and bone sparing therapy for the treatment of destructive arthritis. Recombinant hIL-18BP could therefore represent a new disease-modifying anti-rheumatic drug that warrants testing in clinical trials in patients with rheumatoid arthritis.