title: Does lipophilicity per se induce adjuvant effects? Methyl palmitate as model substance does not affect ovalbumin sensitization.
abstract: 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.
authors: Airway Allergy and Irritation Group, National Institute of Occupational Health, Copenhagen, Denmark. jsh@ami.dk
authors: Jitka Stilund
authors: JS
authors: Hansen
authors: Søren Thor
authors: ST
authors: Larsen
authors: Lars K
authors: LK
authors: Poulsen
authors: Gunnar Damgård
authors: GD
authors: Nielsen
mesh_terms: D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000633:toxicity*; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics; D010168:Palmitates / Q000493:pharmacokinetics / Q000633:toxicity*; D010316:Particle Size; D012119:Respiration / Q000187:drug effects; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000336:Aerosols; D000485:Allergens; D007074:Immunoglobulin G; D010168:Palmitates; D007073:Immunoglobulin E; D010047:Ovalbumin; C019012:methyl palmitate