Effect of ibuprofen on the in vitro and in vivo reactivation of latent HSV-1

Abstract

Prostaglandins have been suggested to play an important role in the reactivation of latent herpes simplex virus. To further understand the role of prostaglandins in the reactivation process, we investigated the effects of ibuprofen, a nonsteroidal anti-inflammatory drug with prostaglandin synthesis inhibitory activity, on the in vitro and in vivo reactivation of latent type 1 herpes simplex virus in mouse ganglia and rabbits, respectively. Ibuprofen, at a concentration of 50 or 100 μM, did not alter the titer of reactivated virus from explanted ganglia with latent virus, but, at a concentration of 200 or 500 μM, it significantly reduced the reactivated viral titer from the ganglia. Ibuprofen also directly inhibited the replication of herpes simplex virus in trigeminal ganglia and Vero cell monolayers, which indicates that the drug reduced the recovery of reactivated viral titers from explanted ganglia with latent virus by acting on the replication process rather than on the reactivation mechanism in vitro. The systemic administration of ibuprofen failed to demonstrate any significant effect on the ocular shedding of virus after attempted reactivation by 6-hydroxydopamine iontophoresis in rabbits with latent herpes simplex virus infection. This failure in vivo could be due to the short half-life and low concentration of ibuprofen at the site of reactivation and replication of latent virus. Alternatively, in the clinical setting, it is conceivable that ibuprofen may not have an effect on in vivo reactivation of latent herpes.