Participation of interleukin-5 and interleukin-8 in the eosinophil migration induced by a large volume of saline.

Recently we demonstrated that the eosinophil migration into rat peritoneal cavities induced by a large volume of saline is mediated by LTB4 released by the resident macrophages and mast cells. In the present study, we have investigated the involvement of IL-5 and IL-8 in this process. We observed that saline-stimulated mast cells released the eosinophil chemotactic cytokines IL-5 and IL-8, while macrophages released only IL-8. These observations were confirmed by the ability of antibodies against IL-5 and IL-8 block the eosinophil chemotactic activity of the mast cell supernatants while the chemotactic activity of the macrophage supernatants was inhibited only by the antibody to IL-8. Recombinant forms of IL-5 and IL-8, when injected intraperitoneally, induced a dose-dependent eosinophil accumulation in naïve rats. The mechanism by which these cytokines induce eosinophil migration seems to be dependent on the resident cell population since depleting the peritoneal cavities of the latter renders the animals unresponsive to the eosinophil recruitment when challenged with IL-5, IL-8 or the supernatants of saline-treated mast cells or macrophages. Dexamethasone and MK 886 blocked the eosinophil migration induced by both the supernatants of saline-stimulated mast cells or macrophages and by IL-5 or IL-8. The IL-5-induced eosinophil migration was also blocked by BW A4C, another lipoxygenase inhibitor. Together, these results suggest LTB4 to be the lipoxygenase metabolite involved in the eosinophil recruitment induced by IL-5 and IL-8. Our results indicate that the eosinophil migration induced by saline is a complex phenomenon which is dependent on the resident mast cells and macrophages and is mediated by LTB4, IL-5 and IL-8. Mast cells release LTB4, IL-5 and IL-8, whereas macrophages release mainly LTB4 and IL-8. The inhibition of one of these mediators (IL-5, IL-8 or LTB4) completely blocked the eosinophil migration induced by saline, suggesting that they act synergistically.