Local anti‐inflammatory activity of steroid‐21‐oate esters in the carrageenan pleurisy model of acute inflammation

Abstract

AbstractLocal anti‐inflammatory activities in the carrageenan (CGN)‐induced pleurisy model are reported for steroid‐21‐oate esters derived from prednisolone. Following administration of equipotent doses (per rat) of prednisolone (P),.5mg; methyl 17,20α‐acetonidodihydroprednisolonate (P4AC), 1 mg; methyl 20β‐dihydroprednisolonate (P4B), 1.3 mg; methyl 20α‐dihydroprednisolonate (P4A), 5.8 mg; and methyl 17,20β‐acetonidodihydroprednisolonate (P4BC), 6 mg, effects of the steroids on exudate volume, leukocyte recruitment, and enzyme levels of cell‐free exudates and washed exudate cells were assessed. All derivatives tested significantly inhibited emigration of neutrophils (PMNs) and monocytes (MNs). Steroid treatment with the β‐isomers reduced exudate volumes by 41% and 56% for P4B and P4BC, respectively. In 5 hr neutrophilic exudates, free β‐glucuronidase levels were reduced by 43% by either P4B or P4AC treatments. Of the derivatives tested P4B and P4AC treatments resulted in the greatest reduction of free lysozyme levels. Activities of membrane‐bound γ‐glutamyl‐transferase (GGTP) in exudate cell pellets were reduced following treatment with P and the 20 alpha‐epimers P4AC and P4A. Systemic effects assessed as decreases in plasma corticosterone or suppression of circulating lymphocytes were noted only following P treatment. These results suggest that 1) the locally active steroid‐21‐oate esters act at the site of inflammation by inhibiting PMN and MN infiltration in a manner congruous with conventional steroids, 2) steroid stereochemical configuration plays a role in effects on exudate volumes and GGTP activities, and 3) due to the absence of systemic effects, the steroid‐21‐oate esters may be safer local anti‐inflammatory agents.