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Repeated daily exposure to 2 ppm nitrogen dioxide upregulates the expression of IL-5, IL-10, IL-13, and ICAM-1 in the bronchial epithelium of healthy human airways
  1. S Pathmanathan1,
  2. M T Krishna1,
  3. A Blomberg2,
  4. R Helleday2,
  5. F J Kelly3,
  6. T Sandström2,
  7. S T Holgate1,
  8. S J Wilson1,
  9. A J Frew1
  1. 1University of Southampton, Southampton, UK
  2. 2University of N. Sweden, Umeå, Sweden
  3. 3The Rayne Institute, St Thomas’ Hospital, London, UK
  1. Correspondence to:
 Dr M T Krishna
 Medical Specialties (RCMB Division), Mail Point 810, Level D, Centre Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; mtkrishna{at}


Background: Repeated daily exposure of healthy human subjects to NO2 induces an acute airway inflammatory response characterised by neutrophil influx in the bronchial mucosa

Aims: To assess the expression of NF-κB, cytokines, and ICAM-1 in the bronchial epithelium.

Methods: Twelve healthy, young non-smoking volunteers were exposed to 2 ppm of NO2/filtered air (four hours/day) for four successive days on separate occasions. Fibreoptic bronchoscopy was performed one hour after air and final NO2 exposures. Bronchial biopsy specimens were immunostained for NF-κB, TNF-α, eotaxin, Gro-α, GM-CSF, IL-5, -6, -8, -10, -13, and ICAM-1 and their expression was quantified using computerised image analysis.

Results: Expression of IL-5, IL-10, IL-13, and ICAM-1 increased following NO2 exposure.

Conclusion: Upregulation of the Th2 cytokines suggests that repeated exposure to NO2 has the potential to exert a “pro-allergic” effect on the bronchial epithelium. Upregulation of ICAM-1 highlights an underlying mechanism for leucocyte influx, and could also explain the predisposition to respiratory tract viral infections following NO2 exposure since ICAM-1 is a major receptor for rhino and respiratory syncytial viruses.

  • nitrogen dioxide
  • bronchial epithelium
  • cytokines
  • ICAM-1
  • Th2 response
  • BHR, bronchial hyperresponsiveness
  • CV, coefficient of variation
  • FEV, forced expiratory volume
  • GMA, glycol methacrylate
  • ICAM, intercellular adhesion molecule
  • IL, interleukin
  • NF, nuclear factor
  • TNF, tumour necrosis factor
  • ROI, reactive oxygen intermediates
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