Optimization of route of administration for coexposure to ovalbumin and particle matter to induce adjuvant activity in respiratory allergy in the mouse.
Epidemiological and experimental studies have not only shown that air pollution induces increased pulmonary morbidity, and mortality, but also that air pollution components may potentiate allergic responses. The respiratory allergy model to ovalbumin in the mouse has been shown a useful tool to characterize the adjuvant potency of air pollution components. However, the choice for the most effective route of administration for testing small amounts of air pollution component is hampered by the diversity of routes of administration used. To test the adjuvant activity of airborne particles (Ottawa dust EHC-93), we studied the optimal route of respiratory administration: intranasally (in) and aerosol (aero) in comparison with responses observed by intraperitoneal (ip) with diesel exhaust particles (DEP) as a positive control. Our results show that the combination of in/aero with ovalbumin caused almost similar immunoglobulin (Ig)E and inflammatory responses compared to the ip/aero. In/in application induced less responses for IgE, less inflammation in the lung, and less increased numbers of eosinophils in the bronchoalveolar lavage (BAL). This response increased dramatically when ovalbumin was coadministered with DEP. Subsequently, EHC-93, which is made up of airborne particles, was tested via the in/in route of administration. EHC-93 induced similar IgE responses, inflammation, and eosinophilic response in BAL compared to DEP. In addition, EHC-93 increased the airway responsiveness of the ovalbumin-sensitized mice measured in unrestrained condition and not in nonsensitized control mice. It is concluded that intranasal sensitization with intranasal challenge with airborne particles (EHC-93) is an effective route of administration to show potency of adjuvant activity of airborne particles.
Laboratory for Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands. p.steerenberg@rivm.nl
P A
PA
Steerenberg
W J
WJ
van Dalen
C E T
CE
Withagen
J A M A
JA
Dormans
H
H
van Loveren
D000281:Administration, Intranasal; D000336:Aerosols; D000393:Air Pollutants / Q000506:poisoning*; D000818:Animals; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D004347:Drug Interactions; D004391:Dust; D004804:Eosinophils / Q000276:immunology; D006967:Hypersensitivity / Q000209:etiology*; D007073:Immunoglobulin E / Q000032:analysis; D007249:Inflammation; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage* / Q000494:pharmacology; D010316:Particle Size; D001335:Vehicle Emissions
D000336:Aerosols; D000393:Air Pollutants; D004391:Dust; D001335:Vehicle Emissions; D007073:Immunoglobulin E; D010047:Ovalbumin