Differential chemokine regulation by Th2 cytokines during human RPE-monocyte coculture.

PURPOSE To determine the effects of the potent anti-inflammatory Th2 cytokines, interleukin (IL)-4, -10, and -13, on IL-8 and monocyte chemoattractant protein (MCP) 1 production by human retinal pigment epithelial (HRPE) cells, monocytes, and HRPE cell-monocyte cocultures. METHODS Enzyme-linked immunosorbent assays were performed to determine IL-8 and MCP-1 secretion by HRPE cells, monocytes, and HRPE cell-monocyte cocultures stimulated with IL-1beta or TNF-alpha, either alone, or in combination with IL-4, -10, or -13, at various time points. RESULTS IL-4 and -13, but not IL-10, enhanced constitutive and TNF-alpha-induced HRPE IL-8 and MCP-1 secretion. IL-4 also enhanced IL-1beta-induced HRPE IL-8. IL-4 and -13 reduced monocyte IL-8 and MCP-1, whereas IL-10 reduced monocyte IL-8 but enhanced MCP-1. Overlay of monocytes onto HRPE cell cultures resulted in increased IL-8 and MCP-1 secretion. IL-8 secretion by HRPE cell-monocyte cocultures was inhibited by IL-4, -10, and -13, whereas MCP-1 was inhibited only by IL-10. These cytokines also inhibited IL-1beta potentiation of IL-8, but not MCP-1 secretion by cocultures. IL-4 enhanced TNF-alpha potentiation of chemokine secretion by cocultures, whereas IL-10 had no effects. IL-13 potentiated TNF-alpha-induced MCP-1, but not IL-8 secretion by cocultures. CONCLUSIONS IL-4, -10 and -13 have complex effects on chemokine secretion by HRPE cells, monocytes, and HRPE cell-monocyte cocultures. IL-10 appears to be the most consistently suppressive cytokine, suggesting potential therapeutic usefulness of IL-10 in the treatment of ocular inflammatory and proliferative diseases.