Studies on novel immunosuppressive agents in experimental arthritis

Abstract: Rheumatoid Arthritis (RA) is a chronic inflammatory disease of the joints. The hallmark of RA is persisting inflammation in diarthrodial joints with infiltration of leukocytes, thickening of the synovial lining layer and synovial pannus formation. The therapeutic aim for RA patients is to alleviate the symptoms, slow the disease progression and optimise the quality of life. In recent years the measures to achieve this goal have improved with the development of new drugs. Despite the recent development of more effective therapies for RA, there is still no drug available that induces remission in all patients. Thus, there is still a need to screen and develop new anti-rheumatic treatments. Because of this we investigated the effects of treatment with compounds which were extracted from three different sources in collagen-induced arthritis (CIA) in Dark Agouti (DA) rats. The constituent of the first compound is dominated by flavonoids together with other extractable compounds derived from Artocarpus leaves. The second compound is Glucuronotixyclomannan (GXM) isolated from culture filtrates of Cryptoccocus neoformans. GXM is a polyssacharide with an unbranched mannose backbone. The third compound, code named Rob 803, is 9-chloro-2,3 dimethyl-6-(N,Ndimetylamino-2-oxoethyl)-6H-indolo [2,3-b] quinoxaline, an analogue of a previously reported substance, B220. B220 was originally investigated as an anti-viral drug. Results: 1. Treatment of rats with the Artocarpus extract decreased arthritis incidence and severity and delayed disease onset. In vitro, the Artocarpus extract acted as a T cell modulator, inhibiting mitogen-induced T cell proliferation and inducing apoptosis of activated cells. A new flavonoid glucoside named artonkin-4'-