STUDIES ON THE ACUTE INFLAMMATORY RESPONSE. III. GLUCOCORTICOIDS AND VITAMIN E (IN VIVO) ATTENUATE THERMAL LABILIZATION OF ISOLATED HEPATIC LYSOSOMES

¹ Department of Pharmacology, Louisiana State University, School of Medicine, New Orleans, Louisiana 70112

An in vivo system was used to study the effects of both steroidal and nonsteroidal anti-inflammatory drugs on lysosomal membranes. Dexamethasone, triamcinolone acetonide, vitamin E and cortisone acetate significantly inhibited thermally induced release of enzymes from lysosomes isolated from liver cells of rats treated with these drugs for three days; indomethacin and phenylbutazone were ineffective. In contrast, both steroids and nonsteroids were effective in attenuating the acute inflammatory response (primary phase) of polyarthritis in rats on days 2 and 4 after inoculation in the subplantar region of the hind paws with adjuvant; nonsteroids block this inflammatory response at dosages ineffective in stabilizing lysosomes of liver cells. Vitamin E has no antiarthritic effects on days 2, 4, 16 or 21 after inoculation at dose levels that markedly stabilize lysosomes. Thus, although the mechanism of anti-inflammatory and antiarthritic action of nonsteroidal drugs remains obscure, that of steroids may be in part through stabilization of lysosomal membranes. However, the results with vitamin E suggest that this need not be a major mechanism even with steroids. Alternatively, the membrane of lysosomes of rat liver may be different from the membrane of cells (e.g., polymorphonuclear leucocytes) which may be involved in the pathogenesis of this inflammatory response, particularly at relevant sites in the actual arthritic rat.