Assessment of antiviral activity, efficacy, and toxicity of prostaglandin A(2) in a rabbit model of herpetic keratitis

Prostaglandin A(2) (PGA(2)) inhibited the replication of herpes simplex virus type 1 in rabbit and human cornea stromal cells at concentrations of 1 to 5 mu M while causing significant toxicity at 55 to 150 mu M Despite favorable therapeutic indices in cultured cells, PGA(2) 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 PGA(2) than in untreated or placebo-treated controls, The recovery of virus from tissues of latently infected rabbits was not affected by therapy, PGA(2) therapy alone induced breakdown of the blood-aqueous barrier, indicating that pharmacologically active concentrations of drug were achieved in the eye, Thus, PGA(2) had antiviral activity, but its proinflammatory effects appeared to be more detrimental than beneficial in the treatment of herpetic keratitis.