Interleukin-4 and melatonin ameliorate high glucose and interleukin-1β stimulated inflammatory reaction in human retinal endothelial cells and retinal pigment epithelial cells

PURPOSE: We aimed to evaluate the effects of two immune regulatory factors, interleukin-4 (IL-4) and melatonin, on several inflammatory mediators that are involved in inflammation and angiogenesis in diabetic retinopathy (DR), in high glucose or interleukin-1β (IL-1β) induced primary human retinal endothelial cells (RECs) and human retinal pigment epithelial (RPE) cells. METHODS: Human RECs and RPE cells were cultured in 30 mM D-glucose or 10 ng/ml IL-1β, with or without the presence of 40 ng/ml IL-4 or 100 μM melatonin. The mRNA and protein levels of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), matrix metalloproteinases 2 (MMP2), and matrix metalloproteinases 9 (MMP9) were measured using real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: High glucose and IL-1β induced the expression of VEGF, ICAM-1, MMP2, and MMP9 in human RECs and RPE cells. IL-4 and melatonin downregulated the expression of VEGF, ICAM-1, MMP2, and MMP9 induced by high glucose and IL-1β. CONCLUSIONS: Our results demonstrated that IL-4 and melatonin inhibited inflammation and angiogenesis triggered by high glucose and IL-1β, which suggests that these immune regulatory factors may be of potential therapeutic value in DR.