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.
Copyright 2003 S. Karger AG, Basel
MeSH terms
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Adjuvants, Immunologic / metabolism*
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Adjuvants, Immunologic / pharmacology
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Anti-Inflammatory Agents / metabolism*
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Anti-Inflammatory Agents / pharmacology
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Calcitonin Gene-Related Peptide / immunology
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Calcitonin Gene-Related Peptide / metabolism
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Calcitonin Gene-Related Peptide / pharmacology
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Cells, Cultured
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Chemotaxis, Leukocyte / drug effects
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Chemotaxis, Leukocyte / immunology
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Down-Regulation / drug effects
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Down-Regulation / immunology
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Eosinophils / drug effects
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Eosinophils / immunology
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Eosinophils / metabolism*
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Granulocyte-Macrophage Colony-Stimulating Factor / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Humans
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Inflammation Mediators / metabolism*
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Inflammation Mediators / pharmacology
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Interleukin-16 / metabolism*
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Interleukin-5 / immunology
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Interleukin-5 / metabolism
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Interleukin-5 / pharmacology
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Neuroimmunomodulation / drug effects
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Neuroimmunomodulation / immunology*
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Neuropeptides / immunology*
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Neuropeptides / metabolism
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Neuropeptides / pharmacology
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Secretogranin II
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Substance P / immunology
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Substance P / metabolism
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Substance P / pharmacology
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Up-Regulation / drug effects
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Up-Regulation / immunology
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Vasoactive Intestinal Peptide / immunology
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Vasoactive Intestinal Peptide / metabolism
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Vasoactive Intestinal Peptide / pharmacology
Substances
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Adjuvants, Immunologic
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Anti-Inflammatory Agents
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Inflammation Mediators
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Interleukin-16
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Interleukin-5
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Neuropeptides
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Secretogranin II
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secretoneurin
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Substance P
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Vasoactive Intestinal Peptide
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Granulocyte-Macrophage Colony-Stimulating Factor
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Calcitonin Gene-Related Peptide