Kinetics of cytokine production in the cornea and trigeminal ganglion of C57BL/6 mice after corneal HSV-1 infection.
To investigate the role of cytokines in the pathogenesis of acute herpetic keratitis (HK), we examined the kinetics of cytokine expression in the corneas and the trigeminal ganglia (TG) of C57BL/6Cr (B6) mice after herpes simplex virus type 1 (HSV-1) infection and observed the influence of the targeted disruption of interferon-gamma (IFN-gamma) gene on the clinical course of HK and/or viral clearance. Following corneal infection with HSV-1 Amakata strain, all corneas developed a typical dendritic keratitis. Quantitative analysis using enzyme-linked immunosorbent assay (ELISA) revealed that the expression of interleukin-1alpha (IL-1alpha), IL-5, IL-6, and IFN-gamma in corneas and TGs significantly elevated immediately after infection, peaked between days 2 and 7 postinfection (p.i.), and then diminished. One exception was IFN-gamma, whose expression significantly persisted in the TGs until day 30 p.i. An additional experiment using IFN-gamma-/- (gko) mice revealed that there was no significant difference in the peak level of viral replication in corneas and TGs between gko and B6 mice, although gko mice showed a significant delay of virus clearance in both corneas and TGs (p < 0.005) and higher mortality rate than B6 mice after HSV-1 infection (p < 0.01). These data suggest that the production of proinflammatory cytokines closely correlates with the pathogenesis of HK, and that IFN-gamma plays an important role in enhancing viral clearance from the cornea and TG.
He
J
J
Department of Microbiology, Kyoto Prefectural University of Medicine, Japan.
Ichimura
H
H
Iida
T
T
Minami
M
M
Kobayashi
K
K
Kita
M
M
Sotozono
C
C
Tagawa
Y I
YI
Iwakura
Y
Y
Imanishi
J
J
D000818:Animals; D003315:Cornea / Q000378:metabolism* / Q000821:virology; D003316:Corneal Diseases / Q000378:metabolism* / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D006561:Herpes Simplex / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000821:virology; D014779:Virus Replication
D016207:Cytokines; D007371:Interferon-gamma