Document Detail


Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis.
MedLine Citation:
PMID:  20442436     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-04
Journal Detail:
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:
Created Date:  2010-08-17     Completed Date:  2010-09-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  540-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Pneumology, University Hospital, Freiburg, Germany. antje.prasse@uniklinik-freiburg.de
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MeSH Terms
Descriptor/Qualifier:
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:
0/Tumor Necrosis Factor-alpha; 0/Vasodilator Agents; 37221-79-7/Vasoactive Intestinal Peptide

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