Synergistic interaction between interferon-alpha and acyclovir in the treatment of herpes simplex virus type 1 infection in mice.
Hairless mice were infected intracutaneously with HSV-1 and treated with rHuIFN-alpha A/D, a recombinant DNA-derived hybrid human interferon-alpha that is active on mouse cells in vitro and in vivo. When given alone (1 or 2 X 10(5) units/dose) at times soon after infection, interferon showed some efficacy, reducing disease severity by 20-30% compared to control. Oral acyclovir was also effective in reducing disease severity in a dose-dependent manner, even when treatment was begun 72 h post-infection after herpetic vesicles had become apparent. When used in combination with acyclovir (400 mg/kg/day beginning 72 h post-infection), rHuIFN-alpha A/D (beginning 4 h post-infection) greatly enhanced the therapeutic effect of the nucleoside, giving a 64% reduction in disease severity score relative to control (compared to 14% for acyclovir alone). Furthermore, although interferon treatment alone was ineffective if begun after disease was apparent, it nonetheless potentiated the activity of acyclovir when co-administered with the nucleoside beginning 72 h post-infection. Combination therapy markedly reduced disease severity, limited the progression of the infection to the vesicular stage in 50% of recipient mice and promoted a more rapid onset of healing than was obtained by treatment with acyclovir alone.
D000212:Acyclovir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy / Q000382:microbiology / Q000628:therapy*; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008812:Mice, Hairless; D011994:Recombinant Proteins; D018139:Simplexvirus / Q000187:drug effects*; D013997:Time Factors
D007370:Interferon Type I; D011994:Recombinant Proteins; D000212:Acyclovir