Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects.
BACKGROUND
Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group.


OBJECTIVE
This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility.


METHODS
Healthy and mild allergic asthmatic subjects (using only inhaled beta2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-alpha, GRO-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), fractalkine and ENA-78.


RESULTS
When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM-CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects.


CONCLUSIONS
The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.
Bosson
J
J
Department of Respiratory Medicine and Allergy, University Hospital, Umeå, Sweden.
Stenfors
N
N
Bucht
A
A
Helleday
R
R
Pourazar
J
J
Holgate
S T
ST
Kelly
F J
FJ
Sandström
T
T
Wilson
S
S
Frew
A J
AJ
Blomberg
A
A
D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000276:immunology*; D016022:Case-Control Studies; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016207:Cytokines / Q000032:analysis*; D004198:Disease Susceptibility; D004848:Epithelium / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000032:analysis; D008297:Male; D010126:Ozone / Q000009:adverse effects*
D000393:Air Pollutants; C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D016207:Cytokines; D015848:Interleukin-5; D016209:Interleukin-8; D015847:Interleukin-4; D010126:Ozone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor