Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers

Several epidemiologic studies have demonstrated a consistent association be tween levels of particulate matter (PM) in the ambient air with increases i n cardiovascular and respiratory mortality and morbidity. Diesel exhaust (D E), in addition to generating other pollutants, Is a major contributor to P M pollution in most places in the world. Although the epidemiologic evidenc e is strong, there are as yet no established biological mechanisms to expla in the toxicity of PM in humans. To determine the Impact of DE on human air ways, we exposed IS healthy human volunteers to air and diluted DE under co ntrolled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy w ere performed 6 h after each exposure to obtain airway lavages and endobron chial biopsies. While standard lung function measures did not change follow ing DE exposure, there was a significant increase in neutrophils and B lymp hocytes in airway lavage, along with increases in histamine and fibronectin . The bronchial biopsies obtained 6 h after DE exposure showed a significan t increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along wi th upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, wi th increases in the numbers of LFA-1+ cells in the bronchial tissue.. Signi ficant increases in neutrophils and platelets were observed In peripheral b lood following DE exposure. This study demonstrates that at high ambient co ncentrations, acute short-term DE exposure produces a well-defined and mark ed systemic and pulmonary inflammatory response In healthy human volunteers , which Is underestimated by standard lung function measurements.