Suppression of acute and chronic inflammation in adrenalectomized rats by pharmacologic amounts of prostaglandins

Abstract

Abstract Prostaglandin E 1 (PGE 1 ) suppressed acute carrageenan‐induced inflammation and chronic joint inflammation characteristic of adjuvant disease in the rat. Placement of PGE 1 into subcutaneous air blebs at the time of carrageenan injection retarded movement of polymorphonuclear leukocytes into the focus of inflammation and produced a concentration‐dependent reduction in exudate β‐glucuronidase and lactate dehydrogenase activities, an effect also observed in adrenalectomized rats. PGE 2 also significantly reduced enzyme activities released into inflammatory exudates. Ultrastructural studies indicated that carrageenan was ingested by invading polymorphs and enclosed within phagocytic vacuoles, the membranes of which subsequently ruptured. More lysosomes remained intact after carrageenan uptake in bleb leukocytes from PGE 1 ‐treated than from control rats and there was no loss of phagosomal membrane integrity in cells from treated rats. Treatment of adrenalectomized rats with PGE 1 (300 μg twice daily) prevented adjuvant‐induced systemic arthritis, reduced the acute inflammatory reaction at the site of adjuvant injection, and reduced the number of circulating small lymphocytes. Together, these two sets of experiments suggest that pharmacologic doses of prostaglandins are anti‐inflammatory in acute and chronic models, and that the effect is not mediated entirely by stimulation of the pituitary and/or adrenal glands.