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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-gamma ), 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-gamma release in vitro by peritoneal cells from uninfected mice, while no appreciable IFN-gamma production was found in uninfected mice administered IL-18. Although IFN-gamma 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-gamma 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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