Inhibition of Endotoxin-Induced Uveitis and Potentiation of Cyclooxygenase-2 Protein Expression by α-Melanocyte–Stimulating Hormone

PURPOSE: The efficacy of alpha-melanocyte-stimulating hormone (alpha-MSH) on endotoxin-induced uveitis (EIU) was investigated in rats. Several studies have demonstrated that there are various inflammatory reactions mediated by an alpha-MSH receptor in macrophages. In addition, as it is known that cyclooxygenase (COX)-2 is induced by a variety of stimuli and plays an important role in inflammation, COX-2 expression was also investigated in macrophage cells treated with alpha-MSH in vitro to clarify its anti-inflammatory effect. METHODS: EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). The number of infiltrating cells and protein concentration in the aqueous humor collected 24 hours after the LPS treatment was determined. The levels of prostaglandin (PG)-E2, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 production were determined. RAW 264.7 cells were pretreated with various concentrations of alpha-MSH for 24 hours and subsequently incubated with 10 microg/mL LPS for 24 hours. COX-2 protein expression was analyzed by Western blot analysis. RESULTS: alpha-MSH suppressed the development of EIU in a dose-dependent fashion. The treatment with alpha-MSH reduced the PGE2, TNF-alpha, IL-6, and MCP-1 concentrations in aqueous humor. The COX-2 protein expression in the alpha-MSH group decreased. CONCLUSIONS: This study suggests that alpha-MSH has an antiocular inflammatory effect, by suppression of PGE2, TNF-alpha, IL-6, and MCP-1 production and blocking of COX-2 expression.