Human corneal interleukin-8. IL-1 and TNF-induced gene expression and secretion

Abstract

Corneal leukocytic infiltration is an important component of numerous ocular diseases, but specific corneal-derived leukocyte chemotaxins have not been identified. In this study, the authors identified interleukin-8 (IL-8), a known neutrophil and lymphocyte chemotaxin, to be an important chemotaxin produced by human corneal tissue. In situ hybridization and immunohistochemistry of corneas exposed to human recombinant (r) interleukin-1-beta (rIL-1 beta) or tumor necrosis factor-alpha (rTNF-alpha) revealed significant increases in corneal endothelial and stromal cell IL-8 mRNA (P less than 0.001) and marked increases in cell-associated immunoreactive IL-8 compared with unstimulated controls. ELISA assays revealed four- to eight-fold increases in corneal IL-8 secretion after 24-hour exposures to either cytokine over that obtained with unstimulated corneas (P = 0.01). In neutrophil chemotactic bioassays, significant increases in functional IL-8 were detected in media conditioned by corneas exposed to rIL-1 beta or rTNF-alpha for 24 hours (P less than 0.001). Preincubation of these corneal media with anti-IL-8 antibody significantly reduced neutrophil chemotaxis by more than 80%. These results suggest that the cornea is an active participant in ocular inflammation and raise the possibility that agents used in experimental corneal pocket models may produce indirect effects by inducing corneal secretion of other factors, such as IL-8.