Objectives: Eosinophils are prominent inflammatory cells that respond to peripheral neuropeptides in vitro and in vivo. At inflammatory sites, cytokines activate distinct cellular and biochemical pathways that act in a coordinated fashion. We investigated whether peripheral neuropeptides can act as immunomodulators by influencing cytokine release from eosinophils. Methods: Human eosinophils were enriched using magnetic cell sorting, and IL-16 levels in supernatants from maintained eosinophils were measured by ELISA. Biological activity of IL-16 was confirmed in lymphocyte chemotaxis assays. Results: Substance P, vasoactive intestinal polypeptide, calcitonin gene-related peptide and secretoneurin reduced the IL-16 release from eosinophils; this effect was additive to that observed with GM-CSF or IL-5. Decreased IL-16 levels in supernatants resulted in reduced lymphocyte chemotaxis, whereas supernatants derived from SP-treated eosinophils stimulated lymphocyte chemotaxis, even though IL-16 was decreased. Conclusions: Results suggest that distinct neuropeptides are able to reduce the number of lymphocytes at inflammatory sites during existing eosinophilia by inhibiting eosinophil IL-16 release, thus attenuating the pro-inflammatory action of lymphocytes and monocytes.

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