Participation of lnterleukin-5 and lnterleukin-8 in the Eosinophil Migration Induced by a Large Volume of Saline

Abstract

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 macro-phage 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 BWA4C, another lipoxyge-nase 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

Airway epithelium expresses interleukin-18

“…This finding was unexpected, however, as previous work has demonstrated that LPS administration is associated with eosinophil infiltration [29]. LPS activation of macrophages has been shown to result in the expression of eosinophil chemoattractants [33, 34] and depletion of these cells has been associated with inhibition of tissue eosinophilia [31]. Furthermore, IL‐18 has been shown to induce the expression of GM‐CSF, an important eosinophil‐related cytokine, from these cells [8].…”

Microbicidal activity of eosinophils is associated with activation of the arginine‐NO pathway

“…Other doses of IL‐5 (20 and 50 ng/ml), Rantes (1 and 3 ng/ml) and TNF‐α (20 and 100 IU/ml) also did not stimulate the nitrite production either alone or in the presence of LPS. This absence of effect of these cytokines is not consequence of species specificity, since the same batch of IL‐5, Rantes and TNF‐α induced eosinophil migration ( Oliveira et al . 1996 ) and hyperalgesia (personal observation) in rats.…”

Eosinophilic alveolitis in BAL after lung transplantation

“…In-vitro studies demonstrated saline induced migration of eosinophils into peritoneum mediated by LTB4 that was released by resident mast cells and macrophages [5]. This process appears to be mediated either by IL-5 inducing a specific eosinophilic migration, or by IL-8 inducing a mixed migration of eosinophils and neutrophils [16]. BAL differential cell count from our study population showed significant amounts of neutrophils, suggesting the possibility of an IL-8 mediated process.…”