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In a previous paper (1) from this laboratory it was shown that a rebound of granu lomatous inflammation of rats took place after withdrawal of glucocorticoid therapy, resulting in a rapid recovery in the wet weight of the granuloma and in the total contents of tissue DNA and non-collagen protein. In an experiment of incorporation of radio active precursors into tissue components in vitro we also observed that the reactivation of DNA synthesis followed the reactivation of non-collagen protein synthesis and the synthetic activity of collagen overtook the control level only at the latest stage in this re bound process. The fact that the synthetic activity of DNA of the granuloma was re covered rapidly in this rebound process suggests that newly formed tissue cells play im portant roles in the course of the reactivation of the granuloma. The present research, therefore, was performed to investigate direct effects of DNA inhibition on the reactiva tion of the granulomatous tissue components. Hydroxyurea, an agent that is known to possess specific inhibitory actions on DNA synthesis with little direct action on the syn thetic activities for RNA and proteins was used. (2-4). Male rats of Donryu strain. 6-7 weeks of age, weighing 130-150g were used. The animals were fed on laboratory chow and water ad libitum and maintained in a fixed-tem perature environment. Granulomatous tissue was induced by injecting a 2 % solution of carrageenin (Marine Colloid Inc., Springfield, N.J., U.S.A.) as described previously (5). Hydrocortisone acetate (Saline suspension (25 mg/ml) was obtained from Nippon Merck Banyu Co. Ltd., Tokyo) was administered directly into the granuloma pouch in the form

INHIBITION BY HYDROXYUREA OF THE REBOUND OF GRANULOMATOUS INFLAMMATION FOLLOWING WITHDRAWAL OF GLUCOCORTICOID THERAPY