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
- S Pathmanathan1,
- M T Krishna1,
- A Blomberg2,
- R Helleday2,
- F J Kelly3,
- T Sandström2,
- S T Holgate1,
- S J Wilson1,
- A J Frew1
- 1University of Southampton, Southampton, UK
- 2University of N. Sweden, Umeå, Sweden
- 3The Rayne Institute, St Thomas’ Hospital, London, UK
- 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}yahoo.com
- Accepted 11 October 2002
Abstract
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.
- 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







