Abstract
Abstract: :
Purpose: To elucidate the effect Cyclosporin A (CyA) and FK506 on cytokine expression in cultured human conjunctival fibroblasts. Methods: Fibroblast cultures from normal conjunctiva were exposed to different concentrations of CyA (0.01–100 µg/ml) and FK506 (0.01–100 µg/ml) for 24 hours with or without interleukin–1α (IL– 1α ) (1 ng/ml). Cell growth was determined at each concentration. Interleukin–6 (IL–6), interleukin–8 (IL–8), transforming growth factor–ß1 (TGF–ß1) and monocyte chemotactic protein–1 (MCP–1) concentrations in culture medium were evaluated by ELISA. Based on the results of ELISA, mRNA expressions of IL–6 and –8 were also quantitated using real–time PCR. Results: CyA (0.01–100 µg/ml) and FK506 (0.01–10 µg/ml) showed no effect on the growth of conjunctival fibroblasts. The 24 hour incubation with IL–1α increased the concentrations of IL–6, –8 and MCP–1 in the supernatans of fibroblast cultures. The concentrations of IL–6 and IL–8 were extremely high in the supernatants of fibroblast cultures with CyA (100 µg/ml). In contrast, MCP–1 in the supernatants of fibroblast cultures with CyA (100 µg/ml) was significantly lower than the controls. TGF–ß1 was not regulated by CyA, and none of the cytokines were changed by the addiditon of FK506. While mRNA of IL–6 and IL–8 was up–regulated by CyA (100 µg/ml), FK 506 showed no effect on the expression of either cytokines. Conclusions: CyA and FK506 showed different effects on human conjunctival fibroblasts. In a clinical situation, the different action of these drugs on conjunctival fibroblasts should be considered.
Keywords: inflammation • cyclosporine • cytokines/chemokines