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 o f tissue damage by various cell types. One important function of IL-8 is to recruit neutrophils into sites of inflammation and to activate t heir biological activity. Stromal keratitis induced by herpes simplex virus type 1 (HSV-1) is characterized by an initial infiltration of ne utrophils. This study was carried out to determine whether cells resid ent in the cornea synthesize IL-8 after virus infection. Pure cultures of epithelial cells and keratocytes established from human corneas we re infected with HSV-1, and the medium overlying the cells was subsequ ently assayed for IL-8 by an enzyme-linked immunosorbent assay. Cytoki ne mRNA levels in cell lysates were monitored by Northern (RNA) blot a nalysis. 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 ma de per 10(6) cells. Neither UV-inactivated virus nor virus-free filtra tes collected from HSV-1-infected keratocytes could induce IL-8 protei n or mRNA, suggesting that viral gene expression was needed for induct ion of IL-8 gene expression. Unlike keratocytes, HSV-1-infected epithe lial cells failed to synthesize IL-8 protein or mRNA. However, these c ells readily produced both molecules following tumor necrosis factor a lpha stimulation. HSV-1 had similar titers in both cell types. Thus, t he 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-infecte d corneal keratocytes to synthesize IL-8 suggests that these cells can contribute to the induction of the acute inflammatory response seen i n herpes stromal keratitis.