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E.D. Varnell, B.M. Gebhardt, H.E. Kaufman, H.W. Thompson, J.M. Hill; COX Inhibitors and Prevention of Ocular Herpes Simplex Recurrences . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4632.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine whether ocular recurrences of herpes simplex virus (HSV) can be prevented or reduced in the mouse, rabbit, and squirrel monkey. Methods: During latency, mice were heat stressed and drug treated. The non-specific COX inhibitor acetylsalicylic acid (aspirin) and the COX-2 inhibitors celecoxib (Celebrex), and 5,5-dimethyl-3-(3-flurophenyl-4-(4-methylsulfonyl)phenyl-2(5H)-furanone (DFU) were given prophylactically or at the time of heat stress. HSV-1 latent rabbits were treated orally with aspirin, celecoxib, or placebo. Starting one month after virus inoculation, squirrel monkeys were randomized to treatment for three days, temperature stressed, and their corneas were examined for signs of recurrences. The monkeys were treated either with intraperitoneal (IP) celecoxib or BSS, or with oral DFU or vehicle. Results. Treatment with acetylsalicylic acid reduced heat stress-induced viral reactivation by an average of 65% compared to placebo-treatment in mice. In mice, prophylaxis with acetylsalicylic acid was more effective than treatment instituted at the time of induction of reactivation. Treatment of latently infected rabbits with oral acetylsalicylic acid resulted in fewer spontaneous recurrences than in rabbits treated with oral placebo. The selective COX-2 inhibitors celecoxib and DFU reduced recurrences in mice by an average of 58% compared to the placebo treatment. Oral celecoxib treatment of latently infected rabbits did not reduce spontaneous or induced reactivation in rabbits. Recurrences were not reduced in squirrel monkeys treated with IP celecoxib. There was less viral DNA in the trigeminal ganglia of mice treated with DFU compared to placebo-treated mice. Oral treatment of 16 squirrel monkeys with either DFU in 1% carboxymethylcellulose (CMC) or 1% CMC showed recurrent corneal lesions in seven control monkeys while only one DFU-treated monkey showed herpetic recurrences - a significant reduction with this highly selective and more potent COX-2 inhibitor. Conclusions: We have found that the nonselective cyclooxygenase inhibitor, acetylsalicylic acid, and the selective cyclooxygenase 2 inhibitor (DFU) significantly inhibit HSV-1 reactivation in hyperthermically stressed mice. The potent, selective cyclooxygenase 2 inhibitor DFU also significantly reduced recurrences of herpetic keratitis in hypothermically stressed primates. The research reported was conducted in compliance with the "ARVO Statement for the Use of Animals in Ophthalmic and Vision Research"
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