Antiviral activity and dose optimum of recombinant macrophage colony-stimulating factor on herpes simplex genitalis in guinea pigs.
The antiviral activity of recombinant human macrophage CSF (M-CSF) against genital herpes simplex virus type-2 (HSV-2) infection in guinea pigs was investigated. M-CSF stimulates proliferation of human and guinea pig peripheral blood monocytes, specifically the plastic adherent esterase-positive mononuclear cells. When anti-HSV-2 activity of M-CSF was evaluated in guinea pigs by 6 daily injection (s.c.) of M-CSF at various doses (5 x 10(5) to 7 x 10(7) U/kg), we found 2 x 10(6) U/kg to be the optimum dose for protective efficacy against primary HSV-2 infection. Either at a lethal, 5 x 10(5) pfu, or sublethal 5 x 10(4) pfu of virus challenge, animals treated with the optimum regimen of M-CSF exhibited lower herpetic lesion scores (p less than 0.005), and lower mortality (p less than 0.025) than animals in placebo group. M-CSF treatment increased the HSV-infected cell killing activities of plastic-adherent mononuclear cells, indicating that in vivo administration of M-CSF may activate the antiviral effects of guinea pig macrophages that may play a role in protection against severity and mortality of herpetic disease.
Ho
R J
RJ
Department of Medicine, Stanford University School of Medicine, CA 94305.
Chong
K T
KT
Merigan
T C
TC
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control*; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects
D000998:Antiviral Agents; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor