Ja. Carr et al., INTERLEUKIN-12 EXHIBITS POTENT ANTIVIRAL ACTIVITY IN EXPERIMENTAL HERPESVIRUS INFECTIONS, Journal of virology, 71(10), 1997, pp. 7799-7803
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.