EFFECTS OF 0.2 PPM OZONE ON BIOMARKERS OF INFLAMMATION IN BRONCHOALVEOLAR LAVAGE FLUID AND BRONCHIAL-MUCOSA OF HEALTHY-SUBJECTS

Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to inves tigate the mechanisms contributing to neutrophil recruitment and to ex amine the role of T-cells in the acute inflammatory response, we expos ed 12 healthy humans to 0,2 parts per million (ppm) of ozone and filte red air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation=30 L(.)min(-1) ). Fibreoptic br onchoscopy was performed 6 h after the end of exposures. Total protein , tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth- related oneogene-alpha (Gro-alpha) mere measured and total and differe ntial cell counts were performed in bronchoalveolar lavage (BAL) fluid , Flow cytometry was performed on BAL cells to study total T-cells, T- cell receptors (alpha beta and gamma delta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+), Using immunohistoche mistry: neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and v ascular adhesion molecule (VCAM)-1 were quantified in the bronchial bi opsies. Paired samples were available from nine subjects, Following oz one exposure there was a threefold increase in the proportion of polym orphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL- 8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0,058), A signific ant positive correlation was demonstrated between the two chemokines a nd proportion of PMNs in BAL fluid. After ozone exposure there was a s ignificant decrease in the CD4/CD8 ratio (p=0,05) and the proportion o f activated CD4+ (p=0,01) and CD8+ T-cells (p=0.04). However, no signi ficant changes were demonstrable in any of the inflammatory markers st udied in the biopsies. Short-term exposure of healthy humans to 0.2 pp m ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. T his response seems to be mediated at least in part by interleukin-8 an d growth-related oncogene-alpha.