title: Cryogenic induced ocular HSV-1 reactivation is enhanced by an inhibitor of the lipoxygenase pathway.
abstract: Reactivation of latent herpes simplex virus type 1 (HSV-1) has been shown to occur in response to localized inflammation. Prostaglandins and lipoxygenase products [eg. hydroxyeicosatetraenoic acids, (HETEs)] are associated with inflammation and, therefore, may play a role in HSV-1 infection and reactivation. In the rabbit cornea, alkali injury, cryogenic injury, and acute HSV-1 infection promote the synthesis of HETEs. Recently, a platelet activating factor antagonist, ginkgolide B (BN 52021) has been found to specifically inhibit the corneal synthesis of HETEs after alkali injury. If the induction of HETEs after injury is related to HSV reactivation and severity of infection, BN 52021 may alter HSV reactivation and the severity of infection by reducing the production of HETEs. To study the effect of BN 52021 on HSV-1 reactivation, cryogenic corneal lesions were produced in ten HSV-1 latently infected rabbits. Five rabbits were treated with topical and intravenous BN 52021 while the remaining five rabbits received topical artificial tears and intravenous saline. In the BN 52021 treated group, 90% (9/10) of the eyes and 53% (35/66) of the total ocular cultures were positive for HSV-1. In the control group, 60% (6/10) of the eyes, and 27% (18/66) of the ocular swabs were positive for HSV-1. The total number of positive cultures was significantly greater (p less than .05) in the BN 52021 treated rabbits. By increasing the number of positive HSV ocular cultures, BN 52021 appeared to act similarly to other inhibitors of arachidonic acid metabolism such as steroidal and nonsteroidal anti-inflammatory agents.
authors.affiliation: Lions Eye Research Laboratories, LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans 70112.
authors.forename: C F
authors.initials: CF
authors.lastname: Beyer
authors.forename: D J
authors.initials: DJ
authors.lastname: Tepper
authors.forename: J M
authors.initials: JM
authors.lastname: Hill
mesh_terms: D000818:Animals; D003315:Cornea / Q000187:drug effects / Q000382:microbiology; D065306:Corneal Injuries; D003452:Cryosurgery; D004224:Diterpenes; D046934:Ginkgolides; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007635:Keratitis, Dendritic / Q000382:microbiology*; D007783:Lactones / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011817:Rabbits; D011897:Random Allocation; D018139:Simplexvirus / Q000187:drug effects / Q000254:growth & development* / Q000302:isolation & purification; D014775:Virus Activation / Q000187:drug effects*; D014776:Virus Cultivation
chemical_list: D004224:Diterpenes; D046934:Ginkgolides; D006893:Hydroxyeicosatetraenoic Acids; D007783:Lactones; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; C045856:ginkgolide B