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Journal of Virology, March 1999, p. 2401-2409, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Interleukin-18 Protects Mice against Acute Herpes
Simplex Virus Type 1 Infection
Noboru
Fujioka,*
Rieko
Akazawa,
Kunihiro
Ohashi,
Mitsukiyo
Fujii,
Masao
Ikeda, and
Masashi
Kurimoto
Fujisaki Institute, Hayashibara Biochemical
Laboratories, Inc., Okayama, Japan
Received 1 June 1998/Accepted 8 December 1998
We examined the effects of interleukin-18 (IL-18) in a mouse model
of acute intraperitoneal infection with herpes simplex virus type 1 (HSV-1). Four days of treatment with IL-18 (from 2 days before
infection to 1 day after infection) improved the survival rate of
BALB/c, BALB/c nude, and BALB/c SCID mice, suggesting innate immunity.
One day after infection, HSV-1 titers were higher in the peritoneal
washing fluid of control BALB/c mice than in that of IL-18-treated
mice. A genetic deficiency of gamma interferon (IFN-
), however,
diminished the survival rate and the inhibition of HSV-1 growth at the
injection site in the mice. Anti-asialo GM1 treatment had no influence
on the protective effect of IL-18 in infected mice. IL-18 augmented
IFN-
release in vitro by peritoneal cells from uninfected mice,
while no appreciable IFN-
production was found in uninfected mice
administered IL-18. Although IFN-
has the ability to induce nitric
oxide (NO) production by various types of cells, administration of the
NO synthase inhibitor
NG-monomethyl-L-arginine resulted
in superficial loss of the improved survival, but there was no
influence on the inhibition of HSV-1 replication at the injection site
in IL-18-treated mice. Based on these results, we propose that IFN-
produced before HSV-1 infection plays a key role as one of the
IL-18-promoted protection mechanisms and that neither NK cells nor NO
plays this role.
*
Corresponding author. Mailing address: 675-1 Fujisaki,
Okayama 702-8006, Japan. Phone: 81-86-276-3141. Fax: 81-86-276-6885.
Journal of Virology, March 1999, p. 2401-2409, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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