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

Abstract

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.

Immunotoxicology of arc welding fume: Worker and experimental animal studies

“…Taken together, the findings of this study were difficult for the authors to resolve given the strong evidence for pro-inflammatory lung effects of a variety of metal-rich particulates such as diesel exhaust, residual oil fly ash, particulate matter, zinc oxide, and coal dust (Blanc et al, 1991;Carter et al, 1997;Salvi et al, 2000;Vallyathan et al, 2000;Ulrich et al, 2002). The authors speculated that the high transitional metal levels in the lung must somehow impair lung host defense and provide a temporary window for infection.…”

Health effects of diesel exhaust emissions

“…This upregulation of endothelial and leukocyte adhesion molecules provides a mechanism for the in¯ux of in¯ammatory cells into the airways. Furthermore, immunohistochemical staining for cytokines has shown enhanced expression of interleukin (IL)-8 and growth related oncogene (GRO)-a in the airway epithelium, which can also play a role in the recruitment of in¯ammatory cells after exposure to DE [31]. The increase in neutrophils in the airway mucosa following exposure to DE was also evident in the bronchial wash, whereas the increase in the number of submucosal mast cells did not correspond to any changes in the number of metachromatic cells (mast cells) in the lavages.…”

Biologic effects of oil fly ash.

“…However, an extrapolation of the body of investigation on ROFA to the health effects of ambient air PM is complicated by the fact that ambient air PM collected from numerous environments has very small amounts of vanadium. Despite this limitation, data continue to accumulate, suggesting that ambient air and other emission source particles follow a comparable mechanism of action as ROFA, involving phosphorylation reactions (54), transcription factor activation (54), mediator release (55), and inflammatory injury (56). …”