| Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. | |
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MedLine Citation:
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PMID: 20442436 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: 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-alpha 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-alpha 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. |
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Authors:
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Antje Prasse; Gernot Zissel; Niklas Lützen; Jonas Schupp; Rene Schmiedlin; Elena Gonzalez-Rey; Anne Rensing-Ehl; Gerald Bacher; Vera Cavalli; Dorian Bevec; Mario Delgado; Joachim Müller-Quernheim |
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Publication Detail:
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Type: Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-04 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 182 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-17 Completed Date: 2010-09-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 540-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Pneumology, University Hospital, Freiburg, Germany. antje.prasse@uniklinik-freiburg.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Inhalation Bronchoalveolar Lavage Fluid / immunology Cells, Cultured Enzyme-Linked Immunosorbent Assay Female Flow Cytometry / methods Follow-Up Studies Humans Male Middle Aged Sarcoidosis, Pulmonary / drug therapy*, immunology* T-Lymphocytes, Regulatory / drug effects, immunology Tumor Necrosis Factor-alpha / drug effects, immunology Vasoactive Intestinal Peptide / immunology*, pharmacology*, therapeutic use Vasodilator Agents / immunology*, pharmacology*, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Tumor Necrosis Factor-alpha; 0/Vasodilator Agents; 37221-79-7/Vasoactive Intestinal Peptide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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