INTERLEUKIN-12 EXHIBITS POTENT ANTIVIRAL ACTIVITY IN EXPERIMENTAL HERPESVIRUS INFECTIONS

The prophylactic and therapeutic efficacy of interleukin-12 was studie d by using murine models of herpes simplex virus infection, Prophylact ic administration consisted of two intraperitoneal doses of interleuki n-12 given 48 and 24 h prior to infection, Therapeutic intraperitoneal administration of interleukin-12 commenced 6 h after the mice were in fected with herpes simplex virus and was continued daily for a total o f 5 days, Interleukin-12 therapy improved the survival rates of mice w ith systemic herpes simplex virus infection compared with those of pla cebo-treated infected mice, Subcutaneous administration of interleukin -12 also improved the rate of survival of mice after systemic herpes s implex virus infection, although higher doses were required to give co mparable effects. Combined prophylactic and therapeutic administration of interleukin-12 produced the greatest effect on survival after an o therwise lethal systemic infection. Intraperitoneal administration of interleukin-12 for 2 days before and 3 days after systemic infection w ith herpes simplex virus resulted in survival of 80% of the mice, Thes e surviving mice were resistant to subsequent reinfection,vith herpes simplex virus, Such resistance was apparently specific for herpes simp lex virus infection, since a second group of survivors succumbed to a lethal infection with murine cytomegalovirus. Infectious virus was rec overed from lumbar ganglia explants dissected from survivors of prophy lactic interleukin-12 therapy and cultured for 5 days in vitro, sugges ting that interleukin-12 treatment did not prevent the establishment o f latent herpes simplex virus infection, One action of interleukin-12 may be to enhance natural killer cell-mediated clearance of the virus, However, interleukin-12 therapy was also effective in mice carrying t he beige mutation, which reduces natural killer cell lytic activity, s uggesting that interleukin-la has additional activities in vivo.