Background: The chemokine eotaxin is a potent and selective chemoattractant for eosinophils. The production of eotaxin by corneal fibroblasts likely contributes to eosinophil infiltration into the corneal stroma. The regulation of eotaxin synthesis in these cells was investigated by examining the effect of interferon-gamma (IFN-gamma), a T helper cell 1-derived cytokine, on eotaxin expression in cultured human corneal fibroblasts.
Methods: The release of eotaxin from cultured corneal fibroblasts was measured by enzyme-linked immunosorbent assay, and the abundance of eotaxin mRNA in these cells was determined by reverse transcription combined with real-time polymerase chain reaction analysis.
Results: IFN-gamma inhibited in a dose-dependent manner the release of eotaxin induced by each of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta in corneal fibroblasts. IFN-gamma also inhibited the increase in the abundance of eotaxin mRNA induced by each of these cytokines. The synergistic increases in eotaxin release and in eotaxin mRNA abundance induced by the combination of TNF-alpha and the T helper cell 2-derived cytokine IL-4 were also both markedly inhibited by the treatment of cells with IFN-gamma.
Conclusions: IFN-gamma inhibited eotaxin expression at both the protein and mRNA levels in cultured human corneal fibroblasts. This effect of IFN-gamma may contribute to the inhibition of eosinophil infiltration into the cornea. Exogenous IFN-gamma thus represents a potential new therapeutic agent for the treatment of corneal disorders associated with inflammatory ocular diseases such as vernal keratoconjunctivitis.
Copyright 2002 S. Karger AG, Basel