MECHANISM OF STEROID ACTION IN OCULAR INFLAMMATION - INHIBITION OF PROSTAGLANDIN PRODUCTION

Abstract

Prostaglandin [PG] E concentration in the aqueous humor of an intact rabbit eye was less than 0.1 ng/ml and increased to 19 .+-. 3 ng/ml 60 min following paracentesis. The rise in PGE level was associated with clinical signs of ocular inflammation. Pretreatment with triamcinolone reduced both the accumulation of PGE in the aqueous humor and the inflammatory response following paracentesis. Intravitreal injection of Escherichia coli endotoxin into rabbit eyes increased PGE level in the anterior chamber to 72 .+-. 17 ng/ml and induced acute uveitis. Slices of iris and ciliary body (ICB) derived from either rabbit eyes with endotoxin-induced uveitis or normal eyes were incubated for 60-240 min and the rate of PGE release into the medium was measured by radioimmunoassay. After a 4 h incubation, PGE release from inflamed ICB was 3-fold higher than that of normal ICB. Incubation of inflamed ICB with hydrocortisone, or Millicorten (100 .mu.g/ml) for 4 h reduced PGE accumulation in the medium by 50 and 81%, respectively. Aldosterone had no effect on the rate of PGE release from inflamed ICB throughout the incubation period. Hydrocortisone or Millicorten also reduced PGE tissue content of inflamed ICB by about 74% during the period of incubation. Indomethacin (100 .mu.g/ml) abolished PGE accumulation. The suppressive action of hydrocortisone on PGE release into the incubation medium was prevented by addition of arachidonic acid (2 .mu.g/ml), a substrate for PG synthesis. The inhibitory action of indomethacin was not affected by provision of arachidonic acid. Glucocorticosteroids probably reduce PGE accumulation by limiting the availability of the substrate for PG biosynthesis and thus suppress the inflammatory response.