Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH) 3 adjuvant

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 day...

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Bibliographic Details
Published in:	Toxicology (Amsterdam) Vol. 184; no. 1; pp. 51 - 68
Main Authors:	Clausen, Susanne Knoth, Bergqvist, Mette, Poulsen, Lars K, Poulsen, Otto Melchior, Nielsen, Gunnar Damgård
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier Ireland Ltd 14-02-2003 Amsterdam Elsevier Science
Subjects:	Adjuvant effect Administration, Inhalation Aerosols Aluminum Hydroxide - pharmacology Animals Atmosphere Exposure Chambers Biological and medical sciences Bronchoalveolar Lavage Fluid - cytology Dose-Response Relationship, Drug Drug Tolerance Experimental and animal immunopathology. Animal models Female General aspects. Methods IgE Immunoglobulin E - biosynthesis Immunoglobulin E - immunology Immunoglobulin G - biosynthesis Immunoglobulin G - immunology Immunopathology Inhalation Injections, Subcutaneous Medical sciences Mice Mice, Inbred BALB C Organ Size - drug effects Ovalbumin - administration & dosage Ovalbumin - immunology Ovalbumin - toxicity Particle Size Respiratory Hypersensitivity - physiopathology Sensitisation Tissue Distribution Tolerance Toxicology Adjuvant effect a.u., arbitrary units BAL, bronchoalveolar lavage IgE Tolerance OVA, ovalbumin PBS, phosphate buffered saline Mice Al(OH) 3, aluminium hydroxide Sensitisation Inhalation RT, room temperature Aluminium hydroxide Ovalbumin Toxicity Chemical compound Interaction Rodentia Vertebrata Mammalia Mouse Immunological adjuvant Animal Aerosols Adjuvant Sensitization Allergen
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Summary:	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.
ISSN:	0300-483X 1879-3185
DOI:	10.1016/S0300-483X(02)00583-8