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Am. J. Respir. Crit. Care Med., Volume 161, Number 2, February 2000, 550-557

Acute Exposure to Diesel Exhaust Increases IL-8 and GRO-alpha Production in Healthy Human Airways

SUNDEEP S. SALVI, CHARLOTTA NORDENHALL, ANDERS BLOMBERG, BERTIL RUDELL, JAMSHID POURAZAR, FRANK J. KELLY, SUSAN WILSON, THOMAS SANDSTRÖM, STEPHEN T. HOLGATE, and ANTHONY J. FREW

Department of Medicine, University of Southampton, Southampton, United Kingdom; Department of Respiratory Medicine and Allergy and Department of Occupational and Environmental Medicine, University Hospital and National Institute for Working Life, Umeå, Sweden; and Cardiovascular Research, The Rayne Institute, St. Thomas Hospital, London, United Kingdom

We have previously demonstrated that short-term exposure to diesel exhaust (DE) for 1 h induced a marked leukocytic infiltration in the airways of healthy human volunteers involving neutrophils, lymphocytes, and mast cells along with increases in several inflammatory mediators. We hypothesized that the leukocyte infiltration and the various inflammatory responses induced by DE were mediated by enhanced chemokine and cytokine production by resident cells of the airway tissue and lumen. To investigate this, 15 healthy human volunteers were exposed to diluted DE and air on two separate occasions for 1 h each in an exposure chamber. Fiberoptic bronchoscopy was performed 6 h after each exposure to obtain endobronchial biopsies and bronchial wash (BW) cells. Using reverse transcriptase/polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR ELISA), a novel and sensitive technique to quantify relative amounts of cytokine mRNA gene transcripts, and immunohistochemical staining with computer-assisted image analysis to quantify expression of cytokine protein in the bronchial tissue, we have demonstrated that DE enhanced gene transcription of interleukin-8 (IL-8) in the bronchial tissue and BW cells along with increases in IL-8 and growth-regulated oncogene-alpha (GRO-alpha ) protein expression in the bronchial epithelium, and an accompanying trend toward an increase in IL-5 mRNA gene transcripts in the bronchial tissue. There were no significant changes in the gene transcript levels of interleukin-1B (IL-1beta ), tumor necrosis factor-alpha (TNF-alpha ), interferon gamma (IFN-gamma ), and granulocyte macrophage colony-stimulating factor (GM-CSF) either in the bronchial tissue or BW cells after DE exposure at this time point. These observations suggest an underlying mechanism for DE-induced airway leukocyte infiltration and offer a possible explanation for the association observed between ambient levels of particulate matter and various respiratory health outcome indices noted in epidemiological studies. Salvi SS, Nordenhall C, Blomberg A, Rudell B, Pourazar J, Kelly FJ, Wilson S, Sandström T, Holgate ST, Frew AJ. Acute exposure to diesel exhaust increases IL-8 and GRO-alpha production in healthy human airways.




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