Modification of immunological responses and clinical disease during topical R-837 treatment of genital HSV-2 infection.
R-837, a compound with no in vitro anti-HSV activity, was administered intravaginally to guinea pigs (5 mg/kg every 12 h) for five days beginning 12 h after genital HSV-2 inoculation. Drug treatment reduced vaginal viral replication (P less than 0.0001), completely protected against primary disease and reduced recurrent genital HSV disease (P less than 0.0001). Drug treatment also induced mild fever, weight loss, and decreased water intake. R-837 was a potent interferon inducer, which also induced variable enhancement of cell-mediated cytolytic activity against HSV-2 targets. Less than 36 h of vaginal HSV shedding was observed in animals with R-837 induced early enhancement of HSV-target cytolysis. Compared to placebo, R-837 decreased ELISA and ADCC antibody to HSV-2, but accelerated HSV-2 specific in vitro IL-2 production and peripheral blood mononuclear cell (PBMC) proliferation. R-837 exhibited potent anti-HSV activity in vivo apparently due to cytokine induction and enhancement of cell-mediated responses.
Harrison
C J
CJ
Children's Hospital Research Foundation, Children's Hospital Medical Center, Cincinnati, Ohio 45229-2899.
Jenski
L
L
Voychehovski
T
T
Bernstein
D I
DI
D000282:Administration, Intravaginal; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000276:immunology; D000077271:Imiquimod; D007111:Immunity, Cellular / Q000187:drug effects; D007372:Interferons / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology; D011897:Random Allocation; D012008:Recurrence; D018139:Simplexvirus / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D014621:Vagina / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects
D000634:Aminoquinolines; D000914:Antibodies, Viral; D000998:Antiviral Agents; D007376:Interleukin-2; D007372:Interferons; D000077271:Imiquimod