The effect of flurbiprofen on herpes simplex virus type 1 stromal keratitis in mice.
The use of steroidal compounds to reduce the inflammation and scarring associated with herpes simplex virus type 1 (HSV-1) stromal keratitis can result in severe exacerbation of the corneal disease. We compared the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen sodium with dexamethasone for the treatment of HSV-1 induced corneal stromal disease in an inbred mouse model. Stromal disease was induced by the direct intrastromal injection of HSV-1. A stromal opacity and corneal neovascularization (CNV) developed in 100% of the injected eyes, with no epithelial involvement until late in the course, when the stromal disease was quite severe, such that it was possible to test the effectiveness of drugs in animals with an intact epithelium. Dexamethasone treatment had a variable effect on the severity of disease, ranging from a significant reduction in severity to significant exacerbation of disease, compared with placebo-treated controls. The most frequent effect of dexamethasone treatment was a worsening of corneal stromal opacities and CNV. In contrast, treatment with the NSAID did not exacerbate HSV-1 stromal disease. Flurbiprofen treatment resulted in a significant reduction of the maximum intensity of stromal opacity in some experiments, whereas in other experiments the effect was not statistically significant. In vitro studies of the effect of the anti-inflammatory drugs on HSV-1 replication in Vero cells revealed that both dexamethasone and flurbiprofen inhibited HSV-1 replication in a dose-dependent manner. Flurbiprofen had a greater inhibitory effect, which appears to be due, at least in part, to a direct virucidal effect. Dexamethasone did not exhibit virucidal activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Hendricks
R L
RL
Department of Ophthalmology, University of Illinois, College of Medicine, Chicago 60612.
Barfknecht
C F
CF
Schoenwald
R D
RD
Epstein
R J
RJ
Sugar
J
J
D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005480:Flurbiprofen / Q000627:therapeutic use*; D007635:Keratitis, Dendritic / Q000188:drug therapy*; D051379:Mice; D008805:Mice, Inbred A; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development; D014709:Vero Cells / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D005480:Flurbiprofen; D003907:Dexamethasone