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Anti-inflammatory effect of THS-201, a new intra-articular steroid
Authors:M Kiniwa  N Yamamoto  Y Hashimoto  H Miyake  H Masuda
Abstract:The effect of THS-201, a new intra-articular steroid, on inflammations was examined using acute, subacute and chronic experimental models, and the antiinflammatory action of THS-201 was compared with those of reference steroids such as triamcinolone acetonide (TA), methylprednisolone acetate (MPA), hydrocortisone acetate (HA) and halopredone (HP). Reference steroids, which were given s.c. or locally, dose-dependently inhibited carrageenin-induced foot-pad edema, sodium carboxymethyl cellulose-induced leukocyte migration, cotton pellet granuloma and carrageenin granuloma pouch in rats. Although the inhibitory effects of reference steroids on such inflammations were unrelated to their administration routes, the inhibitory potency decreased in the following order: TA greater than MPA greater than HA = HP. THS-201 even at a dose of 100 mg/kg had no inhibitory effects on such inflammations when given s.c. By contrast, THS-201 given locally had anti-inflammatory actions: the inhibitory potency of THS-201 in chronic models was higher than that of TA, but was lower in the acute models than that of HA. In antigen-induced arthritis in rabbits, the inhibition of swelling of inflamed joints by intra-articular injection of THS-201 (2 mg/joint) persisted more than 30 days, suggesting that the elimination of THS-201 from the injected site was very slow. In contrast to the finding of reference steroids, THS-201 showed no systemic adverse reactions in all experiments. The results, which are in agreement with the findings of labeled THS-201 into arthritic joints, indicate that THS-201 can strongly inhibit recurrence of inflammation as compared with reference steroids tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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