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Open Access Research article

Aberrant cytokine pattern of the nasal mucosa in granulomatosis with polyangiitis

Janet Wohlers1, Katrin Breucker1, Rainer Podschun2, Jürgen Hedderich3, Peter Lamprecht4, Petra Ambrosch1 and Martin Laudien1*

Author Affiliations

1 University of Kiel, Department of Otorhinolaryngology, Head and Neck Surgery, Arnold-Heller-Straße 14, D-24105 Kiel, Germany

2 Institute for Infection Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Straße 4, D-24105 Kiel, Germany

3 University of Kiel, Department of Medical Informatics and Statistics, Brunswiker Straße 10, D-24105 Kiel, Germany

4 University of Lübeck, Department of Rheumatology, University Hospital of Schleswig-Holstein, Campus Lübeck, and Rheumaklinik Bad Bramstedt, Ratzeburger Allee 160, D-23538 Lübeck, Germany

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Arthritis Research & Therapy 2012, 14:R203  doi:10.1186/ar4041

Published: 17 October 2012

Abstract

Introduction

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.