AIM: Orbital inflammation is common, but the mechanisms underlying leucocytic infiltration of orbital tissue are poorly understood. Human orbital fibroblasts (OF) express chemokines, interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1), when exposed to proinflammatory cytokines. The effect of dexamethasone (DEX) and cyclosporin A (CSA) on OF IL-8 and MCP-1 were examined. METHODS: Cultured human OF were incubated with recombinant interleukin 1 beta (rIL-1 beta; 0.2, 2.0, 20 ng/ml) alone or incubated with rIL-1 beta and DEX (10(-8), 10(-7), 10(-6) M) or CSA (3, 30, 300 ng/ml) for 24 hours. ELISA and northern blot analyses were performed to determine OF IL-8 and MCP-1 protein secretion and mRNA expression, respectively. RESULTS: OF lacked constitutive IL-8 or MCP-1 expression, but secreted significant amounts of these chemokines and expressed substantial steady state mRNA for both chemokines upon rIL-1 beta stimulation. DEX caused dose dependent inhibition of IL-1 induced IL-8 (p < 0.001) and MCP-1 (p < 0.05) secretion and mRNA expression at all concentrations of rIL-1 beta. CSA enhanced IL-1 induced OF IL-8 (p < 0.001) and suppressed rIL-1 beta induced OF MCP-1 (p < 0.05) secretion when lower doses of rIL-1 beta were used. These effects on secreted chemokines at different concentrations of rIL-1 beta and immunomodulating agents were corroborated by steady state OF IL-8 and MCP-1 mRNA expression. CONCLUSIONS: DEX is a potent inhibitor of OF IL-8 and MCP-1. In contrast, CSA enhances IL-1 induced OF IL-8 and suppresses OF MCP-1. These observations may explain the relative lack of CSA effectiveness in human orbital diseases that respond to corticosteroids.
AIM: Orbital inflammation is common, but the mechanisms underlying leucocytic infiltration of orbital tissue are poorly understood. Human orbital fibroblasts (OF) express chemokines, interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1), when exposed to proinflammatory cytokines. The effect of dexamethasone (DEX) and cyclosporin A (CSA) on OF IL-8 and MCP-1 were examined. METHODS: Cultured human OF were incubated with recombinant interleukin 1 beta (rIL-1 beta; 0.2, 2.0, 20 ng/ml) alone or incubated with rIL-1 beta and DEX (10(-8), 10(-7), 10(-6) M) or CSA (3, 30, 300 ng/ml) for 24 hours. ELISA and northern blot analyses were performed to determine OF IL-8 and MCP-1 protein secretion and mRNA expression, respectively. RESULTS: OF lacked constitutive IL-8 or MCP-1 expression, but secreted significant amounts of these chemokines and expressed substantial steady state mRNA for both chemokines upon rIL-1 beta stimulation. DEX caused dose dependent inhibition of IL-1 induced IL-8 (p < 0.001) and MCP-1 (p < 0.05) secretion and mRNA expression at all concentrations of rIL-1 beta. CSA enhanced IL-1 induced OF IL-8 (p < 0.001) and suppressed rIL-1 beta induced OF MCP-1 (p < 0.05) secretion when lower doses of rIL-1 beta were used. These effects on secreted chemokines at different concentrations of rIL-1 beta and immunomodulating agents were corroborated by steady state OF IL-8 and MCP-1 mRNA expression. CONCLUSIONS:DEX is a potent inhibitor of OF IL-8 and MCP-1. In contrast, CSA enhances IL-1 induced OF IL-8 and suppresses OF MCP-1. These observations may explain the relative lack of CSA effectiveness in humanorbital diseases that respond to corticosteroids.
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