Neuropeptide-Induced Inhibition of IL-16 Release from Eosinophils

Abstract

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.

Secretoneurin: A New Player in Angiogenesis and Chemotaxis Linking Nerves, Blood Vessels and the Immune System

“…The chemotactic activity of SN was confirmed by checkerboard analysis, usage of specific polyclonal SN antibodies and receptor desensitisation experiments. In additional experiments, SN was shown further to reduce the release of interleukin-16 from human eosinophils which resulted in reduced lymphocyte chemotaxis in vitro [38].…”

Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review

“…VIP also inhibits the production of IL-6, IL-12, TNF alpha, and nitric oxide, and stimulates IL-10 production, and these effects are mostly mediated through the constitutively expressed VPAC1 receptor at the transcriptional level via modulation of NFκB and cAMP responsive element (CRE)-binding or ets-2 complexes [79]. Dunzendorfer et al have suggested that VIP has an anti-inflammatory effect on eosinophils, reporting that VIP inhibited eosinophil migration and production of IL-16 in vitro , which subsequently inhibited chemotaxis of lymphocytes [80,81]. Delgado et al also reported that VIP inhibited LPS-induced inflammatory pathways in monocytes and macrophages via cAMP-dependent or independent mechanisms [55].…”

Immunomodulation of innate immune responses by vasoactive intestinal peptide (VIP): its therapeutic potential in inflammatory disease

“…VIP is increased in eosinophils isolated from patients with colitis compared to healthy human volunteers [44], but it is not known whether this has any relationship to pathology, or whether up-regulation of VIP in these cells is an attempt to control inflammation homeostatically within the intestinal microenvironment. Dunzendorfer et al [45] have indicated that VIP has an anti-inflammatory effect on eosinophils, reporting that VIP inhibited eosinophil migration and production of IL-16 in vitro [46], which subsequently inhibited chemotaxis of lymphocytes. VIP may therefore inhibit chemotaxis of lymphocytes and monocytes into immune compartments in which eosinophils have migrated in response to parasites or allergens.…”