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

TY - JOUR

T1 - Development of sensitisation or tolerance following repeated OVA inhalation in BALB/cJ mice. Dose-dependency and modulation by the Al(OH)3 adjuvant

AU - Clausen, Susanne Knoth

AU - Bergqvist, Mette

AU - Poulsen, Lars K.

AU - Poulsen, Otto Melchior

AU - Nielsen, Gunnar Damgård

PY - 2003/2/14

Y1 - 2003/2/14

N2 - 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.

AB - 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.

KW - Administration, Inhalation

KW - Aerosols

KW - Aluminum Hydroxide

KW - Animals

KW - Atmosphere Exposure Chambers

KW - Bronchoalveolar Lavage Fluid

KW - Dose-Response Relationship, Drug

KW - Drug Tolerance

KW - Female

KW - Immunoglobulin E

KW - Immunoglobulin G

KW - Injections, Subcutaneous

KW - Mice

KW - Mice, Inbred BALB C

KW - Organ Size

KW - Ovalbumin

KW - Particle Size

KW - Respiratory Hypersensitivity

KW - Tissue Distribution

M3 - Journal article

C2 - 12505376

SN - 0300-483X

VL - 184

SP - 51

EP - 68

JO - Toxicology

JF - Toxicology

IS - 1

ER -