Chemokine synthesis in the HSV-1-infected cornea and its suppression by interleukin-l0

Herpes simplex virus type 1 (HSV-1) infection of the murine cornea results in a tissue-destructive inflammatory response. In this study we show that virus infection induces the synthesis of macrophage inflammatory protein-2 (MIP-2), MIP-1 alpha, and monocyte chemoattractant protein-1 (MCP-1), However, only the production of MIP-2 and MIP-1 alpha coincided with the influx of leukocytes into the cornea. IL-10 treatment markedly suppressed chemokine message and protein synthesis in vivo, Local administration of IL-10 also dramatically reduced the number of T cells and neutrophils migrating into the cornea and suppressed the severity of corneal disease. The inflammatory response could also be suppressed by the passive transfer of neutralizing antibody to MIP-1 alpha but not MCP-1, We conclude that local IL-10 administration can suppress chemokine synthesis, thereby ameliorating corneal disease, Furthermore, our results indicate that MIP-1 alpha plays a major role in herpes stromal keratitis development, whereas MCP-1 does not.