title: Adjuvant and inflammatory effects in mice after subchronic inhalation of allergen and ozone-initiated limonene reaction products.
abstract: Inhalation of ozone (O3), a highly toxic environmental pollutant, produces airway inflammation and exacerbates asthma. However, in indoor air, O3 reacts with terpenes (cyclic alkenes), leading to formation of airway irritating pollutants. The aim of the study was to examine whether inhalation of the reaction products of O3 and the terpene, limonene, as well as limonene and low-level O3 by themselves, induced allergic sensitization (formation of specific immunoglobulin [Ig] E) and airway inflammation in a subchronic mouse inhalation model in combination with the model allergen ovalbumin (OVA). BALB/cJ mice were exposed exclusively by inhalation for 5 d/wk for 2 wk and thereafter once weekly for 12 wk. Exposures were low-dose OVA in combination with O3, limonene, or limonene/O3 reaction products. OVA alone and OVA + Al(OH)3 served as control groups. Subsequently, all groups were exposed to a high-dose OVA solution on three consecutive days. Serum and bronchoalveolar lavage fluid were collected 24 h later. Limonene by itself did not promote neither OVA-specific IgE nor leukocyte inflammation. Low-level O3 promoted eosinophilic airway inflammation, but not OVA-specific IgE formation. The reaction products of limonene/O3 promoted allergic (OVA-specific IgE) sensitization, but lung inflammation, which is a characteristic of allergic asthma, was not observed. In conclusion, the study does not support an allergic inflammatory effect attributed to O3-initiated limonene reaction products in the indoor environment.
authors.affiliation: a National Research Centre for the Working Environment , Copenhagen , Denmark.
authors.forename: Jitka Stilund
authors.initials: JS
authors.lastname: Hansen
authors.forename: Gunnar Damgård
authors.initials: GD
authors.lastname: Nielsen
authors.forename: Jorid Birkelund
authors.initials: JB
authors.lastname: Sørli
authors.forename: Per Axel
authors.initials: PA
authors.lastname: Clausen
authors.forename: Peder
authors.initials: P
authors.lastname: Wolkoff
authors.forename: Søren Thor
authors.initials: ST
authors.lastname: Larsen
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000485:Allergens / Q000633:toxicity*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D053138:Cyclohexenes / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D000077222:Limonene; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D010126:Ozone / Q000633:toxicity*; D013729:Terpenes / Q000633:toxicity*; D059550:Toxicity Tests, Subchronic
chemical_list: D000393:Air Pollutants; D000485:Allergens; D053138:Cyclohexenes; D013729:Terpenes; D007073:Immunoglobulin E; D010126:Ozone; D010047:Ovalbumin; D000077222:Limonene