Assessment of antiviral activity, efficacy, and toxicity of prostaglandin A2 in a rabbit model of herpetic keratitis.
Prostaglandin A2 (PGA2) inhibited the replication of herpes simplex virus type 1 in rabbit and human cornea stromal cells at concentrations of 1 to 5 microM while causing significant toxicity at 55 to 150 microM. Despite favorable therapeutic indices in cultured cells, PGA2 was not effective as a therapeutic agent in the treatment of herpetic keratitis in a rabbit model. The sequelae of disease appeared more severe in animals receiving PGA2 than in untreated or placebo-treated controls. The recovery of virus from tissues of latently infected rabbits was not affected by therapy. PGA2 therapy alone induced breakdown of the blood-aqueous barrier, indicating that pharmacologically active concentrations of drug were achieved in the eye. Thus, PGA2 had antiviral activity, but its proinflammatory effects appeared to be more detrimental than beneficial in the treatment of herpetic keratitis.
O'Brien
W J
WJ
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee 53226, USA. wjob@post.its.mcw.edu
Taylor
J L
JL
Ankel
H
H
Sitenga
G
G
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000821:virology; D011454:Prostaglandins A / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D017154:Stromal Cells / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D012668:Trigeminal Ganglion / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011454:Prostaglandins A; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C100008:prostaglandin A2