Interleukin-18 protects mice against acute herpes simplex virus type 1 infection.
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.
Fujioka
N
N
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Akazawa
R
R
Ohashi
K
K
Fujii
M
M
Ikeda
M
M
Kurimoto
M
M
D000208:Acute Disease; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005677:G(M1) Ganglioside / Q000502:physiology; D006561:Herpes Simplex / Q000517:prevention & control*; D007371:Interferon-gamma / Q000502:physiology; D020382:Interleukin-18 / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009569:Nitric Oxide / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology