Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy

Michel, Olivier; Dentener, Mieke A.; Corazza, Francis; Buurman, Wim A.; Rylander, Ragnar

doi:10.1067/mai.2001.114249

Cited by 87 publications

(97 citation statements)

References 40 publications

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“…To our knowledge, no associations with SNPs located in LBP and atopic phenotypes have been published before. MICHEL et al [33] showed that a rise in serum LBP after LPS inhalation by healthy human individuals was inversely associated with atopic status (defined as high total IgE and skin test positivity) [33]. We hypothesise that SNPs located in LBP alter its expression.…”

Section: Discussionmentioning

confidence: 86%

Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy

Reijmerink¹,

Kerkhof²,

Bottema³

et al. 2011

European Respiratory Journal

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Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system.To assess whether interactions between microbial exposures and genes encoding TLRs (and related genes) result in atopy, genes, environmental factors and gene-environment interactions of 66 single-nucleotide polymorphisms (SNPs) of 12 genes (TLR 1-6, 9 and 10, CD14, MD2, lipopolysaccharide-binding protein (LBP) and Dectin-1), and six proxy parameters of microbial exposure (sibship size, pets (three different parameters), day-care and intrauterine and childhood tobacco smoke exposure) were analysed for association with atopic phenotypes in 3,062 Dutch children (the Allergenic study).The presence of two or more older siblings increased the risk of developing high total immunoglobulin (Ig)E levels at different ages. This risk increased further in children aged 1-2 yrs carrying the minor allele of TLR6 SNP rs1039559. Furthermore, novel two-and three-factor genegene and gene-environment interactions were found (e.g. between sibship size, day-care and LBP SNP rs2232596).Larger sibship size is associated with increased total IgE levels. Furthermore, complex two-and three-factor interactions exist between genes and the environment. The TLRs and related genes interact with proxy parameters of high microbial exposure in atopy development.

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Section: Discussionmentioning

confidence: 86%

Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy

Reijmerink¹,

Kerkhof²,

Bottema³

et al. 2011

European Respiratory Journal

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“…Bronchial challenge studies in healthy subjects further demonstrate that atopy modifi es the human response to endotoxin, with atopic subjects showing signifi cantly decreased systemic infl ammatory responses to inhaled endotoxin compared with nonatopic subjects. 26 It may seem puzzling that classroom-specifi c airborne endotoxin levels were associated with asthma morbidity whereas settled dust levels were not. Th e correlation between classroom-specifi c air and dust endotoxin levels was poor, consistent with other studies performed in the urban setting.…”

Section: Discussionmentioning

confidence: 99%

School Endotoxin Exposure and Asthma Morbidity in Inner-city Children

Lai

Sheehan

Gaffin

et al. 2015

Chest

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“…In addition to eliciting an inflammatory response, LPS induces airway hyperresponsiveness in humans and experimental animals (8,16,17). Given the observed detrimental role of androgens in the inflammatory response to LPS, we sought to determine the potential contribution of androgens to LPS-induced airway hyperresponsiveness.…”

Section: Lps-induced Airway Hyperresponsivenessmentioning

confidence: 99%

Gender Differences in Murine Airway Responsiveness and Lipopolysaccharide-Induced Inflammation

Card

Carey

Bradbury

et al. 2006

The Journal of Immunology

180

137

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The roles of gender and sex hormones in lung function and disease are complex and not completely understood. The present study examined the influence of gender on lung function and respiratory mechanics in naive mice and on acute airway inflammation and hyperresponsiveness induced by intratracheal LPS administration. Basal lung function characteristics did not differ between naive males and females, but males demonstrated significantly greater airway responsiveness than females following aerosolized methacholine challenge as evidenced by increased respiratory system resistance and elastance (p < 0.05). Following LPS administration, males developed more severe hypothermia and greater airway hyperresponsiveness than females (p < 0.05). Inflammatory indices including bronchoalveolar lavage fluid total cells, neutrophils, and TNF-α content were greater in males than in females 6 h following LPS administration (p < 0.05), whereas whole-lung TLR-4 protein levels did not differ among treatment groups, suggesting that differential expression of TLR-4 before or after LPS exposure did not underlie the observed inflammatory outcomes. Gonadectomy decreased airway inflammation in males but did not alter inflammation in females, whereas administration of exogenous testosterone to intact females increased their inflammatory responses to levels observed in intact males. LPS-induced airway hyperresponsiveness was also decreased in castrated males and was increased in females administered exogenous testosterone. Collectively, these data indicate that airway responsiveness in naive mice is influenced by gender, and that male mice have exaggerated airway inflammatory and functional responses to LPS compared with females. These gender differences are mediated, at least in part, by effects of androgens.

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Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy

Cited by 87 publications

References 40 publications

Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy

Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy

School Endotoxin Exposure and Asthma Morbidity in Inner-city Children

Gender Differences in Murine Airway Responsiveness and Lipopolysaccharide-Induced Inflammation

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