Activity of the Keggin polyoxotungstate PM-19 against herpes simplex virus type 2 infection in immunosuppressed mice: role of peritoneal macrophage activation.
The in vivo antiviral activity of the Keggin polyoxotungstate PM-19 [K7(PTi2W10O40).6H2O] against herpes simplex virus type 2 (HSV-2) was investigated in mice immunosuppressed by cyclophosphamide (CY). When PM-19 was administered intraperitoneally to immunosuppressed mice for 3 days (once daily) starting at the time of infection, it prevented death due to HSV-2 encephalitis in a dose-dependent manner (10-25 mg/kg). The in vivo anti-HSV-2 activity of PM-19 was superior to that of acyclovir. Intraperitoneal administration of PM-19 to the immunosuppressed mice significantly increased the number of peritoneal cells, especially macrophages. PM-19 did not stimulate interferon-inducing activity or natural killer cell activity, but markedly enhanced peritoneal macrophage functions: (1) phagocytic activity as assessed by measuring the amount of 51Cr-labeled sheep red blood cells taken into the macrophages, and (2) extrinsic antiviral activity as monitored by reduction in the numbers of plaque formed upon cocultivation of HSV-2-infected HEL cells with the macrophages. These results point to the role of peritoneal macrophage activation in the activity of PM-19 against HSV-2 infection in immunosuppressed mice.
Ikeda
S
S
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Nishiya
S
S
Yamamoto
A
A
Yamase
T
T
Nishimura
C
C
De Clercq
E
E
D000212:Acyclovir / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D002460:Cell Line; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008168:Lung; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D011108:Polymers / Q000627:therapeutic use*; D011863:Radioimmunoassay; D017973:Tungsten Compounds / Q000627:therapeutic use*
D000998:Antiviral Agents; D011108:Polymers; D017973:Tungsten Compounds; C064098:polyoxotungstate PM 19; D000212:Acyclovir