The Control of Lysosomal Enzyme Synthesis and Effects of Steroids

Abstract

Anti-inflammatory effects of adrenal cortical hormones have attracted a great deal of attention during the last decade, especially in connection with rheumatoid arthritis. The following points are well accepted: 1. Rheumatoid synovia contain large numbers of mononuclear cells: lymphocytes (including large pyroninophilic cells, which may be blasts or transformed cells) and macrophages [1, 2]. 2. In cultures of chick embryonic cartilage, release of lysosomal hydrolases following exposure to anti-cellular antibody or other stressing agents brings about the breakdown of matrix. Studies with specific antibody show that cathepsin D plays a major role in this process [3]. It is likely that release of hydrolases from mononuclear cells is also an important cause of cartilage erosion in rheumatoid arthritis [2]. 3. The spontaneous release of lysosomal hydrolases from cultured cells, and that induced by complement-sufficient antibody or ultraviolet light, is in large measure prevented by administration of hydrocortisone [4, 5]. 4. Glucocorticoids diminish the release of hydrolases from isolated lysosomes in vitro under a variety of conditions [6]. These steroids also decrease the redistribution of lysosomal hydrolases which follows the administration of endotoxin [7]. The latter does not necessarily imply intracellular release of hydrolases after endotoxin administration, but the lysosomes may be more readily disrupted by homogenization.