Two distinct IL-18 neutralizing strategies, i.e. a rabbit polyclonal anti-mouse IL-18 IgG and a recombinant human IL-18 binding protein (rhIL-18BP), were used to treat collagen-induced-arthritic DBA/1 mice after clinical onset of disease.The therapeutic efficacy of neutralizing endogenous IL-18 was assessed using different pathological parameters of disease progression.The clinical severity in mice undergoing collagen-induced arthritis was significantly reduced after treatment with both IL-18 neutralizing agents compared to placebo treated mice.Attenuation of the disease was associated with reduced cartilage erosion evident on histology.The decreased cartilage degradation was further documented by a significant reduction in the levels of circulating cartilage oligomeric matrix protein (an indicator of cartilage turnover).Both strategies efficiently slowed disease progression, but only anti-IL-18 IgG treatment significantly decreased an established synovitis.Serum levels of IL-6 were significantly reduced with both neutralizing strategies.In vitro, neutralizing IL-18 resulted in a significant inhibition of TNF-, IL-6, and IFN- secretion by macrophages.These results demonstrate that neutralizing endogenous IL-18 is therapeutically efficacious in the murine model of collagen-induced arthritis.IL-18 neutralizing antibody or rhIL-18BP could therefore represent new disease-modifying anti-rheumatic drugs that warrant testing in clinical trials in patients with rheumatoid arthritis.
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Plater-Zyberk et al. (2001) studied this question.
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