Mechanism of steroid action in ocular inflammation: Inhibition of prostaglandin production.
Prostaglandin E (PGE) concentration the aqueous humor of an intact rabbit eye was less than 0.1 ng. per milliliter and increased to 19 +/- 3 ng. per milliliter 60 minutes 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 E. coli endotoxin into rabbit eyes increases PGE level in the anterior chamber to 72 +/- 17 ng. per milliliter 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 to 240 minutes and the rate of PGE release into the medium was measured by radioimmunoassay. after a 4 hour incubation, the PGE release from inflamed ICB was threefold higher than that of normal ICB. incubation of inflamed ICB with hydrocortisone, or Millicorten (100 mug per milliliter) for 4 hours reduced PGE accumulation in the medium by 50 and 81 per cent, 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 per cent during the period of incubation. Indomethacin (100 mug per milliliter) abolished PGE accumulation. The suppressive action of hydrocortisone on PGE release into the incubation medium was prevented by the addition of arachidonic acid (2 mug per milliliter), a substrate for prostaglandin synthesis. By contrast , the inhibitory action of indomethacin was not affected by provision of arachidonic acid. We suggest that glucocorticosteroids reduce PGE accumulation by limiting the availability of the substrate for prostaglandin biosynthesis and thus suppress the inflammatory response.
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects; D001095:Arachidonic Acids / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D011458:Prostaglandins E / Q000032:analysis / Q000096:biosynthesis*; D011817:Rabbits; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*
D001095:Arachidonic Acids; D004731:Endotoxins; D005938:Glucocorticoids; D011458:Prostaglandins E; D000450:Aldosterone; D006854:Hydrocortisone; D007213:Indomethacin