INDUCTION OF INTERLEUKIN-8 GENE-EXPRESSION IS ASSOCIATED WITH HERPES-SIMPLEX VIRUS-INFECTION OF HUMAN CORNEAL KERATOCYTES BUT NOT HUMAN CORNEAL EPITHELIAL-CELLS

Interleukin-8 (IL-8) is a proinflammatory cytokine released at sites of tissue damage by various cell types. One important function of IL-8 is to recruit neutrophils into sites of inflammation and to activate their biological activity. Stromal keratitis induced by herpes simplex virus type 1 (HSV-1) is characterized by an initial infiltration of neutrophils. This study was carried out to determine whether cells resident in the cornea synthesize IL-8 after virus infection. Pure cultures of epithelial cells and keratocytes established from human corneas were infected with HSV-1, and the medium overlying the cells was subsequently assayed for IL-8 by an enzyme-linked immunosorbent assay. Cytokine mRNA levels in cell lysates were monitored by Northern (RNA) blot analysis. It was found that virus infection of keratocyte cultures led to the synthesis of IL-8-specific mRNA with more than 30 ng of IL-8 made per 10(6) cells. Neither UV-inactivated virus nor virus-free filtrates collected from HSV-1-infected keratocytes could induce IL-8 protein or mRNA, suggesting that viral gene expression was needed for induction of IL-8 gene expression. Unlike keratocytes, HSV-1-infected epithelial cells failed to synthesize IL-8 protein or mRNA. However, these cells readily produced both molecules following tumor necrosis factor alpha stimulation. HSV-1 had similar titers in both cell types. Thus, the failure to induce IL-8 synthesis was not due to an inability of the virus to replicate in epithelial cells. The capacity of HSV-1-infected corneal keratocytes to synthesize IL-8 suggests that these cells can contribute to the induction of the acute inflammatory response seen in herpes stromal keratitis.