Does lipophilicity per se induce adjuvant effects?: Methyl palmitate as model substance does not affect ovalbumin sensitization

Jitka Stilund Hansen; Søren Thor Larsen; Lars K. Poulsen; Gunnar Damgård Nielsen

doi:10.1080/15287390600755083

Does lipophilicity per se induce adjuvant effects? Methyl palmitate as model substance does not affect ovalbumin sensitization

Jitka Stilund Hansen, Søren Thor Larsen, Lars K. Poulsen, Gunnar Damgård Nielsen

9 Citations (Scopus)

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.

Original language	English
Journal	Journal of Toxicology and Environmental Health. Part A: Current Issues
Volume	70
Issue number	2
Pages (from-to)	128-37
Number of pages	10
ISSN	1528-7394
DOIs	https://doi.org/10.1080/15287390600755083
Publication status	Published - 2007

Keywords

Adjuvants, Immunologic
Aerosols
Allergens
Animals
Bronchoalveolar Lavage Fluid
Female
Gastrointestinal Tract
Immunoglobulin E
Immunoglobulin G
Leukocyte Count
Mice
Mice, Inbred BALB C
Ovalbumin
Palmitates
Particle Size
Respiration
Respiratory Hypersensitivity
Respiratory System

Access to Document

10.1080/15287390600755083

Cite this

Does lipophilicity per se induce adjuvant effects? Methyl palmitate as model substance does not affect ovalbumin sensitization. / Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K. et al.

In: Journal of Toxicology and Environmental Health. Part A: Current Issues, Vol. 70, No. 2, 2007, p. 128-37.

Research output: Contribution to journal › Journal article › Research › peer-review

@article{6e37ce2512864f2298d38516436ed386,

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.",

keywords = "Adjuvants, Immunologic, Aerosols, Allergens, Animals, Bronchoalveolar Lavage Fluid, Female, Gastrointestinal Tract, Immunoglobulin E, Immunoglobulin G, Leukocyte Count, Mice, Mice, Inbred BALB C, Ovalbumin, Palmitates, Particle Size, Respiration, Respiratory Hypersensitivity, Respiratory System",

author = "Hansen, {Jitka Stilund} and Larsen, {S{\o}ren Thor} and Poulsen, {Lars K.} and Nielsen, {Gunnar Damg{\aa}rd}",

year = "2007",

doi = "10.1080/15287390600755083",

language = "English",

volume = "70",

pages = "128--37",

journal = "Journal of Toxicology and Environmental Health. Part A: Current Issues",

issn = "1528-7394",

publisher = "Taylor & Francis",

number = "2",

}

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 -

Does lipophilicity per se induce adjuvant effects? Methyl palmitate as model substance does not affect ovalbumin sensitization

Abstract

Keywords

Access to Document

Fingerprint

Cite this