Adjuvant and Inflammatory Effects in Mice After Subchronic Inhalation of Allergen and Ozone-Initiated Limonene Reaction Products

• Published in: Journal of Toxicology and Environmental Health, Part A Vol. 76; no. 19; pp. 1085 - 1095
• Main Authors: Hansen, Jitka Stilund, Nielsen, Gunnar Damgård, Sørli, Jorid Birkelund, Clausen, Per Axel, Wolkoff, Peder, Larsen, Søren Thor
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-10-2013; Taylor & Francis Ltd
• Subjects: Administration, Inhalation; Air Pollutants - toxicity; Allergens - toxicity; Animals; Asthma; Asthma - chemically induced; Asthma - immunology; Body Weight; Bronchoalveolar Lavage Fluid - cytology; Cyclohexenes - toxicity; Disease Models, Animal; Environmental quality; Female; Hazardous air pollutants; Human exposure; Immunoglobulin E - blood; Inflammation - chemically induced; Inflammation - immunology; Inflammation - pathology; Lung - drug effects; Lung - metabolism; Mice; Mice, Inbred BALB C; Ovalbumin - adverse effects; Ovalbumin - immunology; Ozone; Ozone - toxicity; Respiration; Terpenes - toxicity; Toxicity Tests, Subchronic
• ISSN: 1528-7394; 1087-2620; 2381-3504
• DOI: 10.1080/15287394.2013.838915

Inhalation of ozone (O
3
), a highly toxic environmental pollutant, produces airway inflammation and exacerbates asthma. However, in indoor air, O
3
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 O
3
and the terpene, limonene, as well as limonene and low-level O
3
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 O
3
, limonene, or limonene/O
3
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 O
3
promoted eosinophilic airway inflammation, but not OVA-specific IgE formation. The reaction products of limonene/O
3
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 O
3
-initiated limonene reaction products in the indoor environment.