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Treatment of adjuvant arthritis with antibradykinin drugs

The discovery of the polypeptides of the bradykinin type has made possible an additional approach to the problem of mediation of inflammatory reaction. Besides such mediators as histamine and 5-hydroxytryptamine, bradykinin could be responsible for some syndromes of inflammation particularly for the pathogenesis of the delay phase of the reactions (Turk & Willoughby, 1969). We now present the results of experiments on bradykininogen and the influence of some antibradykinin drugs on the course of rheumatic-like pathology in rats. Both the induction procedure and the gradation of its course were described by Pelczarska (1969). To estimate the level of bradykininogen in blood plasma in adjuvant-treated rats, seven groups of eight randomly bred Wistar rats were used. The animals were injected with complete Freund adjuvant and at appropriate intervals each group of animals was bled. Bradykininogen levels were estimated according to Diniz, Carvalho & others (1961). Group I: animals in the induction phase of immunological response (24 h after injection of adjuvant) ; Group I1 : animals in the latent period of the condition (7th day) ; Groups 111-V : rats in the period of full manifestation of the condition (17th, 22nd, and 30th day, respectively); Group VI : after recovery (40th day) ; Control group (non-arthritic rats). The results for bradykininogen are shown in Fig. 1A. To test the therapeutic effects of anti-inflammatory drugs, possessing antibradykinin activity, adjuvant-treated rats of randomly bred Wistar strain were treated with indomethacin (1 mg/kg, orally), sodium phenylbutazone (8 mg/kg, i.p.), amidopyrine (3 mg/kg, i.p.) and sodium salicylate (65 mg/kg, orally). The drugs were administered one day before Freund adjuvant and then three times weekly. The results are in Fig. 1B. The following pattern of examination was used.