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Differential Chemokine Regulation by Th2 Cytokines during Human RPE–Monocyte Coculture

¹ From the Departments of Ophthalmology (W. K. Kellogg Eye Center) and ² Pathology, University of Michigan, Ann Arbor.

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-1ß or TNF-, 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-–induced HRPE IL-8 and MCP-1 secretion. IL-4 also enhanced IL-1ß–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-1ß potentiation of IL-8, but not MCP-1 secretion by cocultures. IL-4 enhanced TNF- potentiation of chemokine secretion by cocultures, whereas IL-10 had no effects. IL-13 potentiated TNF-–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.

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