Inhalation of low-dose endotoxin favors local TH2 response and primes airway phagocytes in vivo

Alexis, Neil E.; Lay, John C.; Almond, Martha; Peden, David B.

doi:10.1016/j.jaci.2004.09.002

Cited by 55 publications

(25 citation statements)

References 23 publications

(17 reference statements)

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“…Intravenous challenge with endotoxin is associated with decreased HRV (associated with increased risk for cardiac events), systemic inflammation, and increases in serum triglycerides and VLDL in human volunteers and in animal models (Godin et al 1996; Goldstein et al 1995; Hardardottir et al 1995; Hudgins et al 2003; Levels et al 2003; Voss et al 2004). We and others have found that bronchial challenge with endotoxin induces systemic inflammatory effects as well, even at inhaled doses that do not cause overt airway or systemic symptoms (Alexis et al 2004; Michel et al 1992, 1997). We have also observed reduced airway cytokine and macrophage responses in healthy volunteers when they were exposed to coarse PM that had been heated to deactivate biologic agents (including denature endotoxin) versus PM that had not been heated (Alexis et al 2006).…”

Section: Discussionmentioning

confidence: 84%

“…Adachi et al (2006) found that intraperitoneally administered endotoxin decreases heart rate variability measures such as rMSSD (root mean square of successive differences in normal-to-normal R-R intervals) and spectral density at low and high frequencies in a mouse model. Moreover, we and others have found that bronchial challenge with endotoxin also induces systemic inflammatory effects in asthmatics, even at inhaled doses that do not cause overt airway or systemic symptoms (Alexis et al 2004; Michel et al 1992, 1997). …”

mentioning

confidence: 72%

“…Pre-bronchodilator values were used. Induced sputum was performed according to previously published procedures (Alexis et al 2001, 2004, 2005), and airway inflammation measures included enumeration of inflammatory cells (neutrophils, eosinophils, monocytes, macrophages). Flow cytometry was performed using a FACSORT (Becton Dickinson, Franklin Lakes, NJ) as previously described (Alexis et al 2005, 2006).…”

Section: Methodsmentioning

confidence: 99%

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Coarse Particulate Matter (PM _2.5–10 ) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma

Yeatts

Svendsen

Creason

et al. 2007

Environ Health Perspect

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143

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IntroductionWe investigated whether markers of airway and systemic inflammation, as well as heart rate variability (HRV) in asthmatics, change in response to fluctuations in ambient particulate matter (PM) in the coarse [PM with aerodynamic diameter 2.5–10 μm (PM2.5–10)] and fine (PM2.5) size range.MethodsTwelve adult asthmatics, living within a 30-mile radius of an atmospheric monitoring site in Chapel Hill, North Carolina, were followed over a 12-week period. Daily PM2.5–10 and PM2.5 concentrations were measured separately for each 24-hr period. Each subject had nine clinic visits, at which spirometric measures and peripheral blood samples for analysis of lipids, inflammatory cells, and coagulation-associated proteins were obtained. We also assessed HRV [SDNN24HR (standard deviation of all normal-to-normal intervals in a 24-hr recording), ASDNN5 (mean of the standard deviation in all 5-min segments of a 24-hr recording)] with four consecutive 24-hr ambulatory electrocardiogram measurements. Linear mixed models with a spatial covariance matrix structure and a 1-day lag were used to assess potential associations between PM levels and cardiopulmonary end points.ResultsFor a 1-μg/m3 increase in coarse PM, SDNN24HR, and ASDNN5 decreased 3.36% (p = 0.02), and 0.77%, (p = 0.05) respectively. With a 1-μg/m3 increase in coarse PM, circulating eosinophils increased 0.16% (p = 0.01), triglycerides increased 4.8% (p = 0.02), and very low-density lipoprotein increased 1.15% (p = 0.01). No significant associations were found with fine PM, and none with lung function.ConclusionThese data suggest that small temporal increases in ambient coarse PM are sufficient to affect important cardiopulmonary and lipid parameters in adults with asthma. Coarse PM may have underappreciated health effects in susceptible populations.

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Section: Discussionmentioning

confidence: 84%

mentioning

confidence: 72%

Section: Methodsmentioning

confidence: 99%

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Coarse Particulate Matter (PM _2.5–10 ) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma

Yeatts

Svendsen

Creason

et al. 2007

Environ Health Perspect

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143

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“…The effect of endotoxin exposure on human allergic disease is even more complex, since the levels of endotoxin vary considerably in different environmental settings. Low doses of endotoxin that are subthreshold for inducing airway neutrophilia seem to result in a Th2 skewed airway inflammatory response in humans [21]. However, a recent experimental study addressing the question how inhalation of low-dose LPS affects the immediate- and late-phase bronchial and inflammatory response in cat allergic asthmatic patients failed to detect any significant effect of exposure to LPS prior to allergen challenge [22].…”

Section: Introductionmentioning

confidence: 99%

Low Levels of Endotoxin Enhance Allergen-Stimulated Proliferation and Reduce the Threshold for Activation in Human Peripheral Blood Cells

Veličković

Thunberg

Polović

et al. 2007

Int Arch Allergy Immunol

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Background: Endotoxins, comprised of bacterial cell wall lipopolysaccharides (LPS), have been reported to have both protective and exacerbating effects on the development and maintenance of allergic disease in humans and on markers of allergic inflammation in animal models of allergy. In this study, we investigated the effect of low concentrations of LPS on human peripheral blood mononuclear cells (PBMC) stimulated with the major cat allergen Fel d 1. Methods: Extensive purification of recombinant (r) Fel d 1 yielded essentially endotoxin-free rFel d 1 (0.2 ng LPS /mg protein). PBMCs prepared from 15 subjects having IgE to cat (>0.7 kU_A/l) and 8 subjects IgE negative to cat were stimulated with 2, 10 or 25 µg/ml of rFel d 1 in the presence or absence of 50 pg/ml LPS. Proliferation was measured after 7 days of culture and supernatants were analyzed for IFNγ, IL-5 and IL-10. Results: LPS (50 pg/ml) increased rFel d 1-stimulated proliferation of PBMCs both from subjects IgE-positive and subjects negative to cat allergens. PBMCs from 13 of the subjects did not proliferate in response to stimulation with 2 and 10 µg/ml rFel d 1 alone but did so in the presence of LPS. Moreover, LPS increased the levels of rFel d 1-stimulated IFNγ in cultures from cat-negative subjects, IL-5 from cat-positive subjects and IL-10 from both groups. Conclusion: Very low doses of LPS enhance proliferation and decrease the apparent threshold level for cell activation, prompting careful evaluation of allergen stimulated T cell activation in vitro.

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“…Toll-like receptor 4 (TLR4) is the predominant and best-characterized cell-surface receptor specific for endotoxin that also might modulate the allergic response. 10–12 Mice deficient in TLR4 and challenged with ovalbumin have increased numbers of lung dendritic cells and higher titers of IgE and airway eosinophils, all markers of atopic asthma, 13 compared with wild-type mice with normal levels of TLR4. Immune downregulation by TLR4 is mediated in part through regulatory T cells, and LPS treatment increases CD4 + CD25 + cell suppressor efficiency by 10-fold, without requiring antigen-presenting cells.…”

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confidence: 99%

Association of Toll-like receptor 4 alleles with symptoms and sensitization to laboratory animals

Pacheco

Maier

Silveira

et al. 2008

Journal of Allergy and Clinical Immunology

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Background Researchers and technicians working with laboratory animals (LAs) are exposed to animal allergen and endotoxin, which can interact to potentiate or inhibit symptoms or allergic responses. We hypothesized that functional genetic variants of Toll-like receptor 4 (TLR4), a key surface receptor for endotoxin, interface between worker and workplace and affect animal sensitization, symptoms, or both. Objective We sought to determine whether TLR4/8551 variants alter the risk for LA sensitization, symptoms, or both. Methods Three hundred thirty-five researchers, 195 of whom worked with animals, completed questions on workplace practices and symptoms and underwent skin prick tests or RASTs to common and animal allergens. Real-time PCR assessed TLR4/8551 and TLR4/8851 variants. Nominal logistic regression was used to analyze the contribution of demographic, exposure, and genetic variables to outcomes of interest. Results Twenty-one percent of workers were LA sensitized, and 29% reported 1 or more symptoms to LAs. The TLR4/8551 G variant, which is less responsive to endotoxin, was detected in 9% and in linkage disequilibrium with the TLR4/8851 T allele. The G variant significantly associated with atopy and LA sensitization. Workers with the G variant spent significantly longer hours in high endotoxin/animal allergen tasks compared with those with the AA variant, which is perhaps less affected by endotoxin exposures. In multivariate analyses the G variant and longer animal research hours increased the risk of LA sensitization. Job tasks and LA sensitization, but not TLR4 variants, were predictors of LA-induced symptoms. Conclusion Workers with TLR4 variants that reduce responsiveness to endotoxin have higher risks for LA and other allergen sensitization but spend longer hours in tasks with high endotoxin and animal allergen exposures.

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Inhalation of low-dose endotoxin favors local TH2 response and primes airway phagocytes in vivo

Cited by 55 publications

References 23 publications

Coarse Particulate Matter (PM _2.5–10 ) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma

Coarse Particulate Matter (PM _2.5–10 ) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma

Low Levels of Endotoxin Enhance Allergen-Stimulated Proliferation and Reduce the Threshold for Activation in Human Peripheral Blood Cells

Association of Toll-like receptor 4 alleles with symptoms and sensitization to laboratory animals

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Inhalation of low-dose endotoxin favors local TH2 response and primes airway phagocytes in vivo

Cited by 55 publications

References 23 publications

Coarse Particulate Matter (PM 2.5–10 ) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma

Coarse Particulate Matter (PM 2.5–10 ) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma

Low Levels of Endotoxin Enhance Allergen-Stimulated Proliferation and Reduce the Threshold for Activation in Human Peripheral Blood Cells

Association of Toll-like receptor 4 alleles with symptoms and sensitization to laboratory animals

Contact Info

Product

Resources

About

Coarse Particulate Matter (PM _2.5–10 ) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma

Coarse Particulate Matter (PM _2.5–10 ) Affects Heart Rate Variability, Blood Lipids, and Circulating Eosinophils in Adults with Asthma