Combinations of antiviral and anti-inflammatory preparations for the topical treatment of herpes simplex virus assessed using a murine zosteriform infection model.
Recently we have reported a zosteriform murine infection model which employs the adoptive transfer of immune cells (ATI) to recipient infected mice to produce a disease that mimics human recurrent herpes simplex virus (HSV) disease. Mice were infected with HSV-1 by scarification at the lateroventral line of the neck; 2 days later, the mice received immune cells from HSV-1-infected syngeneic mice. Although virus was cleared more quickly from the target tissues of virus replication in recipient mice, ATI resulted in a heightened inflammatory response and delayed healing. This model was used to test the effects of topical formulations containing foscarnet and/or the anti-inflammatory agent, hydrocortisone. Virus clearance and clinical signs, including ear thickness and zosteriform spread of lesions, were studied. Treatment with 3% foscarnet accelerated virus clearance but had little effect on clinical parameters. By contrast, 0.5% hydrocortisone increased the titre and extended the presence of infectious virus for at least 6 days, although the reduction in clinical signs was greater than that obtained with topical foscarnet. Foscarnet in combination with hydrocortisone produced a marked reduction in clinical signs while virus replication was reduced. These results are discussed in relation to the inflammation and discomfort experienced by patients and a possible role for anti-inflammatory formulations in the treatment of HSV reactivation episodes in man.
Awan
A R
AR
Centre for Veterinary Science, University of Cambridge, UK. hjf10@cam.ac.uk
Harmenberg
J
J
Flink
O
O
Field
H J
HJ
D000287:Administration, Topical; D019264:Adoptive Transfer; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D017245:Foscarnet / Q000008:administration & dosage / Q000494:pharmacology*; D006561:Herpes Simplex / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D004338:Drug Combinations; D017245:Foscarnet; D006854:Hydrocortisone