Early cytokine synthesis in the excised mouse cornea.

Corneas excised from normal BALB/c mice and incubated in vitro were analyzed for the production of "early-warning" cytokines via reverse transcription-polymerase chain reaction and ELISA. It was found that the trauma of excision stimulated rapid IL-1 alpha synthesis, with peak protein accumulation occurring at 6 h, whereas IL-6 synthesis was maximal at 18 h. Neither IL-1 beta protein nor message was detected at any point, and TNF-alpha synthesis never increased above constituted levels. Antibody neutralization of endogenous IL-1 alpha blocked IL-6 synthesis. Addition of exogenous IL-1 alpha induced IL-1 alpha and IL-6 synthesis in vitro. Inoculation of IL-1 alpha into the cornea induced IL-6 synthesis in vivo. Addition of IL-1 alpha could stimulate IL-1R, IL-1 alpha, and IL-6 mRNA synthesis in the epithelial, stromal, and endothelial components of the cornea. However, protein production was readily detected only in the epithelial layer. We concluded that mechanical trauma to the mouse cornea triggers the enhanced synthesis of IL-1 alpha and IL-1R, which in turn results in the production of IL-6 and more IL-1 alpha. That corneal excision did not stimulate the synthesis of IL-1 beta or TNF-alpha indicates that there is a selective induction of early cytokine expression in this specialized tissue.