title: Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.affiliation: Department of Pneumology, University Hospital, Freiburg, Germany. antje.prasse@uniklinik-freiburg.de
authors.forename: Antje
authors.initials: A
authors.lastname: Prasse
authors.forename: Gernot
authors.initials: G
authors.lastname: Zissel
authors.forename: Niklas
authors.initials: N
authors.lastname: Lützen
authors.forename: Jonas
authors.initials: J
authors.lastname: Schupp
authors.forename: Rene
authors.initials: R
authors.lastname: Schmiedlin
authors.forename: Elena
authors.initials: E
authors.lastname: Gonzalez-Rey
authors.forename: Anne
authors.initials: A
authors.lastname: Rensing-Ehl
authors.forename: Gerald
authors.initials: G
authors.lastname: Bacher
authors.forename: Vera
authors.initials: V
authors.lastname: Cavalli
authors.forename: Dorian
authors.initials: D
authors.lastname: Bevec
authors.forename: Mario
authors.initials: M
authors.lastname: Delgado
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
mesh_terms: D000280:Administration, Inhalation; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology; D014660:Vasoactive Intestinal Peptide / Q000276:immunology* / Q000494:pharmacology* / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000276:immunology* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D014660:Vasoactive Intestinal Peptide