Abstract

Glucocorticoid therapy induced rapid involution of chronic granulomatous inflammation in rats by subcutaneous injection of carrageenin. Hydrocortisone acetate injected into the granuloma pouch at doses higher than 3 mg/kg/day for 3 days caused maximum involution. After withdrawal of the corticoid therapy, rebound of the granulomatous inflammation took place resulting in rapid recovery of the wet weight and total content of tissue DNA and non-collagen proteins. A dose of 3 mg/kg/day was optimal for observing this rebound phenomenon. In order to investigate metabolic aspects of the rebound phenomenon minced granuloma was incubated in vitro with [ 3H] thymidine or [ 3H] proline. The rate of incorporation of the labeled precursor into non-collagen protein was elevated near to the normal level by 24 hr after the interruption of the corticoid treatment. A second step in the course of the recovery was a rapid increase in the incorporation of labeled thymidine into DNA which was attained by 48 hr after the last injection of the corticoid. The rate of recovery of the total amount of non-collagen protein, however, was rather slow compared with that of DNA which reached the control level 3 days after the withdrawal of the corticoid therapy. The total non-collagen protein of the granuloma reached almost complete recovery 1 day later. These results suggest that the synthesis of some fractions of the granuloma proteins which involve proteins essential for DNA synthesis was activated before the reactivation of the synthesis of DNA and some other proteins. Recovery of collagen synthesis was not complete until 4 days after the cessation of the corticoid treatment. Consequently, the total amount of collagen was still lower than that of the control on the last day of the experiment.

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