Acute exposure to diesel exhaust increases IL-8 and GRO-alpha production in healthy human airways

We have previously demonstrated that short-term exposure to diesel exhaust (DE) for 1 h induced marked leukocytic infiltration in the airways of healt hy human volunteers involving neutrophils, lymphocytes, and mast cells alon g with increases in several inflammatory mediators. We hypothesized that th e 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 huma n volunteers were exposed to diluted DE and air on two separate occasions f or 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-li nked immunosorbent assay (RT-PCR ELISA), a novel and sensitive technique to quantify relative amounts of cytokine mRNA gene transcripts, and immunohis tochemical staining with computer-assisted image analysis to quantify expre ssion of cytokine protein in the bronchial tissue, we have demonstrated tha t DE enhanced gene transcription of interleukin-8 (IL-8) in the bronchial t issue and BW cells along with increases in IL-8 and growth-regulated oncoge ne-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-1 beta), tumor necrosis factor-alpha (TNF-alp ha), interferon gamma (IFN-gamma), and granulocyte macrophage colony-stimul ating factor (GM-CSF) either in the bronchial tissue or BW cells after DE e xposure at this Lime point, These observations suggest an underlying mechan ism for DE-induced airway leukocyte infiltration and offer a possible expla nation for the association observed between ambient levels of particulate m atter and various respiratory health outcome indices noted in epidemiologic al studies.