title: Aberrant cytokine pattern of the nasal mucosa in granulomatosis with polyangiitis.
abstract: BACKGROUND
  In granulomatosis with polyangiitis (GPA), a complex autoimmune small-vessel vasculitis frequently associated with chronic necrotizing inflammation of the nasal mucosa, elevated nasal Staphylococcus (S.) aureus carrier rates are a risk factor for relapse. As cytokines are primarily involved in the regulation of defense against potentially pathogenic microorganisms, the aim of this study was to compare healthy individuals and GPA patients with respect to their baseline cytokine expression of nasal epithelial cells (NEC), which form the first barrier against such triggers. The ability of S. aureus to influence the nasal microenvironment's cytokine secretion was assessed by exemplary stimulation experiments.
  
  
  METHODS
  Baseline expression of 19 cytokines of primary NEC of GPA patients and normal controls (NC) was quantified by a multiplex cytokine assay. Stimulation experiments were performed with supernatants of S. aureus and expression of interleukin-8 was determined by ELISA.
  
  
  RESULTS
  In GPA, an altered pattern of baseline cytokine expression with significantly up-regulated G-CSF and reduced interleukin (IL)-8 concentrations was observed. Both NEC of GPA patients and NC responded to stimulation with S. aureus, but GPA patients displayed a significantly lower IL-8 secretion and a diminished dynamic range of response towards the stimulus.
  
  
  CONCLUSIONS
  The data presented underline the hypothesis of a disturbed epithelial nasal barrier function in GPA. The dysregulated baseline expression of G-CSF and IL-8 and the reduced response to microbial stimulation may facilitate changes in the composition of the nasal flora and favour an imbalanced inflammatory response, which might be relevant for the disease course.
authors.forename: Janet
authors.initials: J
authors.lastname: Wohlers
authors.forename: Katrin
authors.initials: K
authors.lastname: Breucker
authors.forename: Rainer
authors.initials: R
authors.lastname: Podschun
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hedderich
authors.forename: Peter
authors.initials: P
authors.lastname: Lamprecht
authors.forename: Petra
authors.initials: P
authors.lastname: Ambrosch
authors.forename: Martin
authors.initials: M
authors.lastname: Laudien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D014890:Granulomatosis with Polyangiitis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000502:physiology; D055815:Young Adult
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D016179:Granulocyte Colony-Stimulating Factor