The effect of modulating the synthesis of arachidonic acid cascade products on HSV lesion recurrence.
Induction of HSV lesion recurrence may be achieved by a variety of stimuli. Trauma of almost any kind (physical, chemical, electromagnetic and thermal) to the healed primary lesion site has been successful for induction of recurrence. In common with each of these mechanisms is the release of inflammatory mediators (arachidonic acid (AA), complement, kinins, etc.) following trauma. Because blockade of the AA cascade with steroids has been noted to abort HSV skin lesions, and because steroids have numerous side effects making them a poor therapeutic choice in ocular lesions, we decided to test several relatively different types of AA cascade inhibitory drugs in mouse ear HSV recurrence models. In this series of experiments, it was found that topical steroids gave the greatest initial decrease in lesion number (80% fewer than control on day 3 post recurrence induction (PRI), while meclofenamate resulted in the greatest reduction of lesions by day 5 PRI (85% fewer lesions than control and 60% fewer than the steroid treated group). The NDGA treated group exhibited the least reduction in recurrence severity (27% fewer lesions than control on day 5 PRI and 200% more lesions than the steroid group. Chlorpromazine (thorazine) acted roughly equivalent to the steroid treated group by day 5 PRI (70% fewer lesions than the untreated control group). Relative efficacy in lesion reduction between groups by day 5 PRI is: meclofenamate greater than steroid = chlorpromazine greater than NDGA greater than control. Meclofenamate, steroid and chlorpromazine significantly reduced lesions (p less than .05) when compared with the saline treated control mice. NDGA did not significantly reduce lesions by day 5 PRI.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001623:Betamethasone / Q000031:analogs & derivatives / Q000627:therapeutic use; D002746:Chlorpromazine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D004423:Ear; D006561:Herpes Simplex / Q000188:drug therapy / Q000473:pathology*; D009637:Masoprocol / Q000627:therapeutic use; D008469:Meclofenamic Acid / Q000627:therapeutic use; D051379:Mice; D012008:Recurrence
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D008469:Meclofenamic Acid; D009637:Masoprocol; D003907:Dexamethasone; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone; D002746:Chlorpromazine