title: Amelioration of ozone-induced lung injury by anti-tumor necrosis factor-alpha.
abstract: Ozone (O(3)) is a significant component of atmospheric air pollution and produces detrimental effects in the lung. Although the mechanism of O(3)-induced lung inflammation and injury is unclear, the increased release of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) by lung cells following O(3) exposure may shed some light on this subject. To investigate the role of TNF-alpha in the O(3)-induced pulmonary insult, we intraperitoneally injected rats with either rabbit preimmune serum or rabbit antirat TNF-alpha 1 h prior to O(3) exposure. Approximately 12 h after the end of O(3) 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 O(3)-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-1alpha, IL-6, and IL-10 in animals exposed to O(3). The gene expression was downregulated in animals treated with anti-TNF-alpha antibody prior to O(3) exposure. The results suggest a central role for TNF-alpha in the mechanistic pathways critical to lung inflammation. The significance of TNF-alpha in the inflammation and epithelial injury produced by ozone exposure reflects its overall contribution through modulation of other cytokines.
authors.affiliation: Department of Occupational and Environmental Health Sciences, College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48202, USA. ad6268@wayne.edu
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Bhalla
authors.forename: Paul G
authors.initials: PG
authors.lastname: Reinhart
authors.forename: Cheng
authors.initials: C
authors.lastname: Bai
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D000418:Albumins / Q000032:analysis; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000235:genetics; D005353:Fibronectins / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D040081:Protein Array Analysis; D011817:Rabbits / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000418:Albumins; D019138:Antibodies, Blocking; D016207:Cytokines; D005353:Fibronectins; D007074:Immunoglobulin G; D010083:Oxidants, Photochemical; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone