Innate defense mechanisms of the nasal airway

Henrik Widegren

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Allergic and infectious rhinitis are prevalent conditions that besides a direct morbidity also causes exacerbations of asthma and chronic obstructive pulmonary disease. The immune mechanisms associated with various forms of rhinitis are not fully understood. The principal aim of this thesis was to examine innate immune mechanisms relevant to allergic and viral rhinitis focusing on the mediators tumour necrosis factor-α (TNFα), Clara cell protein 10 (CC10), and leukotriene B4 (LTB4).

TNFα is a pro-inflammatory cytokine. Intranasal TNFα challenges were performed on healthy subjects and patients with allergic rhinitis. Symptom scores, nasal lavages, nasal peak inspiratory flow, and nasal biopsies demonstrated that 10 µg of topical TNFα caused a non-acute exudative inflammation, further characterized by neutrophil recruitment and activation. TNFα did not affect the responsiveness to allergen in patients with allergic rhinitis.

CC10 is an anti-inflammatory protein mediator produced in the respiratory epithelium. Allergic airway conditions have been associated with low levels of CC10 in the mucosa and plasma. Repeated nasal administrations of CC10 were administered to patients with allergic rhinitis. CC10 did neither affect symptoms of allergic rhinitis nor signs of eosinophil exudative inflammation in this artificial pollen season model.

LTB4 is a lipid mediator involved in the innate immune response. We demonstrated that nasal LTB4 challenge produced neutrophil activation and α-defensin production, without symptoms or exudative inflammation. Furthermore, LTB4-treated neutrophils exerted anti-viral effects in vitro. Finally, repeated nasal intervention with LTB4 did not prevent symptoms produced by human rhinovirus 16 inoculations.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Otorhinolaryngology (Lund)
Supervisors/Advisors
  • Greiff, Lennart, Supervisor
  • Korsgren, Magnus, Supervisor
Award date2010 May 12
Publisher
ISBN (Print)978-91-86443-67-2
Publication statusPublished - 2010

Bibliographical note

Defence details

Date: 2010-05-12
Time: 13:00
Place: Segerfalksalen, BMC A, Lund

External reviewer(s)

Name: Howarth, Peter
Title: Dr
Affiliation: University of Southampton

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Subject classification (UKÄ)

  • Otorhinolaryngology

Free keywords

  • neutrophils
  • Leukotriene B4
  • CC10
  • TNF-alpha
  • innate immunity
  • allergic rhinitis
  • Airway inflammation

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