IL-4 differentially regulates eotaxin and MCP-4 in lung epithelium and circulating mononuclear cells

To investigate the mechanisms of eosinophil recruitment in allergic airway inflammation, we examined the effects of interleukin (IL)-4, a Th2-type cyt okine, on eotaxin and monocyte chemoattractant protein-4 (MCP-4) expression in human peripheral blood mononuclear cells (PBMCs; n = 10), in human lowe r airway mononuclear cells (n = 5), in the human lung epithelial cell lines A549 and BEAS-2B, and in human cultured airway epithelial cells. IL-4 inhi bited eotaxin and MCP-4 mRNA expression induced by IL-1 beta and tumor necr osis factor-alpha in PBMCs but did not significantly inhibit expression in epithelial cells. Eotaxin and MCP-4 mRNA expression was not significantly i nduced by proinflammatory cytokines in lower airway mononuclear cells. IL-1 beta -induced eotaxin and MCP-4 protein production was also inhibited by I L-4 in PBMCs, whereas IL-4 enhanced eotaxin protein production in A549 cell s. In contrast, dexamethasone inhibited eotaxin and MCP-4 expression in bot h PBMCs and epithelial cells. The divergent effects of IL-4 on eotaxin and MCP-4 expression between PBMCs and epithelial cells may create chemokine co ncentration gradients between the subepithelial layer and the capillary spa ces that may promote the recruitment of eosinophils to the airway in Th2-ty pe responses.