Ozone enhancement of lower airway allergic inflammation is prevented by gamma-tocopherol.
Ozone is a commonly encountered environmental oxidant which has been linked to asthma exacerbation in epidemiological studies. Ozone induces airway inflammation and enhances response to inhaled allergen. It has been suggested that antioxidant therapy may minimize the adverse effects of ozone in asthma. We have previously shown that the antioxidant gamma-tocopherol (gammaT), an isoform of vitamin E, also has anti-inflammatory effects. We employed a Brown Norway rat model of ozone-enhanced allergic responses to test the therapeutic effects of gammaT on O(3)-induced airway inflammation. Ovalbumin (OVA)-sensitized rats were intranasally challenged with 0 or 0.5% OVA on Days 1 and 2, and exposed to 0 or 1 ppm ozone (8 h/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg gammaT on Days 2 through 5. Pulmonary tissue and bronchoalveolar lavage fluid (BALF) were collected on Day 6. OVA challenge caused increased total cells (267% increase) and eosinophils (4000%) in BALF that was unaffected by ozone exposure. Morphometric evaluation of lung tissue revealed increases in intraepithelial mucosubstances (IM) (300%) and subepithelial eosinophils (400%) in main axial airways. Ozone exposure of allergic rats enhanced IM increases in proximal axial airways (200%), induced cys-leukotrienes, MCP-1, and IL-6 production in BALF, and upregulated expression of IL-5 and IL-13 mRNA. gammaT treatment had no effect on IM increases by allergen, but blocked enhancement by ozone. gammaT attenuated both OVA- or ozone-stimulated eosinophilic infiltration, and increases of BALF cys-leukotrienes, MCP-1, and IL-6, as well as IL-5 and IL-13 mRNA. These data demonstrate broad anti-inflammatory effects of a gammaT and suggest that it may be an effective therapy of allergic airway inflammation.
Wagner
James G
JG
Department of Pathobiology and Diagnostic Investigation, Michigan State University, 211 Food Safety and Toxicology Building, East Lansing, MI 48824, USA. wagnerja@msu.edu
Jiang
Qing
Q
Harkema
Jack R
JR
Illek
Beate
B
Patel
Dhavalkumar D
DD
Ames
Bruce N
BN
Peden
David B
DB
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D010047:Ovalbumin; D010126:Ozone; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000473:pathology / Q000648:ultrastructure; D024504:gamma-Tocopherol / Q000097:blood / Q000627:therapeutic use*
D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D015289:Leukotrienes; D010126:Ozone; D024504:gamma-Tocopherol; D010047:Ovalbumin