Neuropeptide-induced inhibition of IL-16 release from eosinophils.
OBJECTIVE
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.
Dunzendorfer
Stefan
S
Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria.
Feistritzer
Clemens
C
Enrich
Barbara
B
Wiedermann
Christian J
CJ
D000276:Adjuvants, Immunologic / Q000378:metabolism* / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000494:pharmacology; D019410:Interleukin-16 / Q000378:metabolism*; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology*; D009479:Neuropeptides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D053381:Secretogranin II; D013373:Substance P / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D019410:Interleukin-16; D015848:Interleukin-5; D009479:Neuropeptides; D053381:Secretogranin II; C081159:secretoneurin; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015740:Calcitonin Gene-Related Peptide