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Title

Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis

AuthorsPrasse, A.; Zissel, G.; Lützen, N.; Schupp, J.; Schmiedlin, R.; González-Rey, Elena; Rensing-Ehl, A.; Bacher, G.; Cavalli, V.; Bevec, D.; Delgado, M.; Müller-Quernheim, J.
Issue Date2010
PublisherAmerican Thoracic Society
CitationAmerican Journal of Respiratory and Critical Care Medicine 182: 540- 548 (2010)
AbstractRationale: Previous studies suggest an important immunoregulatory role of vasoactive intestinal peptide (VIP) in experimental models of chronic noninfectious inflammation. Sarcoidosis is characterized by noncaseating epitheloid cell granulomas, where excessive tumor necrosis factor-α production by pulmonary macrophages plays a critical role in granuloma formation and disease progression, which may lead to fatal organ dysfunction. Objectives: To test whether inhaled VIP has an immunoregulatory role. Sarcoid alveolitis was used as a prototype of immune-mediated chronic lung inflammation. Methods: In an open clinical phase II study, we treated 20 patients with histologically proved sarcoidosis and active disease with nebulized VIP for 4 weeks. Measurements and Main Results: VIP inhalation was safe, well-tolerated, and significantly reduced the production of tumor necrosis factor-α by cells isolated from bronchoalveolar lavage fluids of these patients. VIP treatment significantly increased the numbers of bronchoalveolar lavage CD4 +CD127-CD25+ T cells, which showed regulatory activities on conventional effector T cells. In vitro experiments demonstrated the capacity of VIP to convert naive CD4+CD25- T cells into CD4+CD25+FoxP3+ regulatory T cells, suggesting the generation of peripheral regulatory T cells by VIP treatment. Conclusions: This study is the first to show the immunoregulatory effect of VIP in humans, and supports the notion of inhaled VIP as an attractive future therapy to dampen exaggerated immune responses in lung disorders. Thus, the inhalation of neuropeptides may be developed into a new therapeutic principle for chronic inflammatory lung disorders in humans.
URIhttp://hdl.handle.net/10261/83789
DOI10.1164/rccm.200909-1451OC
Identifiersdoi: 10.1164/rccm.200909-1451OC
issn: 1073-449X
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