Journal Article

Amelioration of Ozone-Induced Lung Injury by Anti-Tumor Necrosis Factor-α

Deepak K. Bhalla, Paul G. Reinhart, Cheng Bai and Suresh K. Gupta

in Toxicological Sciences

Volume 69, issue 2, pages 400-408
Published in print October 2002 | ISSN: 1096-6080
Published online October 2002 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/69.2.400
Amelioration of Ozone-Induced Lung Injury by Anti-Tumor Necrosis Factor-α

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Ozone (O3) is a significant component of atmospheric air pollution and produces detrimental effects in the lung. Although the mechanism of O3-induced lung inflammation and injury is unclear, the increased release of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) by lung cells following O3 exposure may shed some light on this subject. To investigate the role of TNF-α in the O3-induced pulmonary insult, we intraperitoneally injected rats with either rabbit preimmune serum or rabbit antirat TNF-α 1 h prior to O3 exposure. Approximately 12 h after the end of O3 exposure the animals were sacrificed, the lungs lavaged, and tissue samples collected for expression of cytokine genes relevant to inflammation. The bronchoalveolar lavage fluid (BALF) was analyzed for albumin as a marker of pulmonary epithelial permeability changes and for fibronectin for its role in lung injury and repair. The lavage cells were collected, counted, and identified to quantitate the inflammatory response. Ozone exposure resulted in a significant increase in BALF albumin and fibronectin as compared to air-exposed controls and a significant increase in BALF polymorphonuclear leukocytes (PMNs). Antibody treatment produced a significant decrease in BALF albumin and PMNs as compared to O3-exposed rats given preimmune serum. Antibody treatment did not affect the BALF fibronectin concentration or the total cell count in the BAL. Tissue analysis for gene arrays revealed an activation of IL-1α, IL-6, and IL-10 in animals exposed to O3. The gene expression was downregulated in animals treated with anti-TNF-α antibody prior to O3 exposure. The results suggest a central role for TNF-α in the mechanistic pathways critical to lung inflammation. The significance of TNF-α in the inflammation and epithelial injury produced by ozone exposure reflects its overall contribution through modulation of other cytokines.

Keywords: tumor necrosis factor-α; permeability; lung; inflammation; cytokines; rats

Journal Article.  5425 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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