title: Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH)3 adjuvant.
abstract: Anthropogenically induced exposures may, due to their adjuvant effect, promote development of sensitisation to commonly occurring aeroallergens. No generally accepted model exists for determination of adjuvant effect of airborne substances. Therefore, BALB/cJ mice were exposed for 10 consecutive days with ovalbumin (OVA) solution, 25 mg/l-10 g/l (0.0025-1%) for 20 min/day, with and without the Al(OH)(3) adjuvant (0.5%). Four days after the last aerosol exposure, no OVA specific IgE and only low IgG1 were produced. Subsequent parenteral OVA administration showed that the 10 g/l solution induced full tolerance of the IgE response, whereas only partial tolerance was apparent with 25 mg/l OVA. The Al(OH)(3) adjuvant counteracted development of tolerance that was fully prevented at the 25 mg/l OVA concentration. Development of IgG1 was increased in a concentration-dependent manner with 500 mg/l-10 g/l OVA. No increase occurred at the 25 mg/l level, but addition of Al(OH)(3) increased IgG1 production to the same level as the higher OVA concentrations. Concentrations from 1.25 mg/l to 10 g/l OVA were studied with ten exposures followed by once-weekly aerosol exposure for uptil 6 weeks. In the range from 1.25 mg/l to 10 g/l, IgE production was time- and concentration-dependent. Both the IgE and IgG1 production were markedly promoted by Al(OH)(3). However, with aerosol exposures, the IgE antibody productions were not sufficient to increase the level of inflammatory cells in broncho-alveolar lavage fluid. Overall, this study showed that airborne Al(OH)(3) was able to counteract tolerance and increase specific IgE and IgG1 production.
authors.affiliation: Department of Chemical Working Environment, National Institute of Occupational Health, Lersø Parkallé 105, DK-2100, Copenhagen, Denmark
authors.forename: Susanne Knoth
authors.initials: SK
authors.lastname: Clausen
authors.forename: Mette
authors.initials: M
authors.lastname: Bergqvist
authors.forename: Lars K
authors.initials: LK
authors.lastname: Poulsen
authors.forename: Otto Melchior
authors.initials: OM
authors.lastname: Poulsen
authors.forename: Gunnar Damgård
authors.initials: GD
authors.lastname: Nielsen
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D010316:Particle Size; D012130:Respiratory Hypersensitivity / Q000503:physiopathology; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D000536:Aluminum Hydroxide; D010047:Ovalbumin