TY - JOUR
T1 - Does lipophilicity per se induce adjuvant effects?
T2 - Methyl palmitate as model substance does not affect ovalbumin sensitization
AU - Hansen, Jitka Stilund
AU - Larsen, Søren Thor
AU - Poulsen, Lars K.
AU - Nielsen, Gunnar Damgård
PY - 2007
Y1 - 2007
N2 - Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled compound induces immunomodulatory effects was investigated in a murine inhalation model with the highly lipophilic methyl palmitate (MP) as model substance. First, studies of acute effects following a 1-h exposure of up to 348 mg/m3 MP showed no effects on cell composition in bronchoalveolar lavage (BAL) or on lung function parameters. Thus, MP did not possess irritant or inflammatory properties, which may be a precursive stimulus for adjuvant effects. Second, mice were exposed to aerosols of MP, 6 or 323 mg/m3, for 1 h followed by a 20-min low-dose ovalbumin (OVA) inhalation. OVA only and OVA + Al(OH)3 served as control groups. Exposures were performed 5 times/wk for 2 wk followed by a weekly exposure for 10 wk. Finally, the mice were challenged with a high-dose OVA aerosol for 3 consecutive days. Neither OVA-specific immunoglobulin (Ig) G1, IgE, or IgG2a production, nor inflammatory cells in BAL, nor respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is, additional structural properties are required.
AB - Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled compound induces immunomodulatory effects was investigated in a murine inhalation model with the highly lipophilic methyl palmitate (MP) as model substance. First, studies of acute effects following a 1-h exposure of up to 348 mg/m3 MP showed no effects on cell composition in bronchoalveolar lavage (BAL) or on lung function parameters. Thus, MP did not possess irritant or inflammatory properties, which may be a precursive stimulus for adjuvant effects. Second, mice were exposed to aerosols of MP, 6 or 323 mg/m3, for 1 h followed by a 20-min low-dose ovalbumin (OVA) inhalation. OVA only and OVA + Al(OH)3 served as control groups. Exposures were performed 5 times/wk for 2 wk followed by a weekly exposure for 10 wk. Finally, the mice were challenged with a high-dose OVA aerosol for 3 consecutive days. Neither OVA-specific immunoglobulin (Ig) G1, IgE, or IgG2a production, nor inflammatory cells in BAL, nor respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is, additional structural properties are required.
KW - Adjuvants, Immunologic
KW - Aerosols
KW - Allergens
KW - Animals
KW - Bronchoalveolar Lavage Fluid
KW - Female
KW - Gastrointestinal Tract
KW - Immunoglobulin E
KW - Immunoglobulin G
KW - Leukocyte Count
KW - Mice
KW - Mice, Inbred BALB C
KW - Ovalbumin
KW - Palmitates
KW - Particle Size
KW - Respiration
KW - Respiratory Hypersensitivity
KW - Respiratory System
U2 - 10.1080/15287390600755083
DO - 10.1080/15287390600755083
M3 - Journal article
C2 - 17365573
SN - 1528-7394
VL - 70
SP - 128
EP - 137
JO - Journal of Toxicology and Environmental Health. Part A: Current Issues
JF - Journal of Toxicology and Environmental Health. Part A: Current Issues
IS - 2
ER -