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It has been established that ingestion of a high-fat diet increases the blood levels of lipopolysaccharides (LPS) from Gram-negative bacteria in the gut. Obesity is characterised by low-grade systemic and adipose tissue inflammation. This is suggested to be implicated in the metabolic syndrome and obesity. In the present review, we hypothesise that LPS directly and indirectly participates in the inflammatory reaction in adipose tissue during obesity. The experimental evidence shows that LPS is involved in the transition of macrophages from the M2 to the M1 phenotype. In addition, LPS inside adipocytes may activate caspase-4/5/11. This may induce a highly inflammatory type of programmed cell death (i.e. pyroptosis), which also occurs after infection with intracellular pathogens. Lipoproteins with or without LPS are taken up by adipocytes. Large adipocytes are more metabolically active and potentially more exposed to LPS than small adipocytes are. Thus, LPS might be involved in defining the adipocyte death size and the formation of crown-like structures. The adipocyte death size is reached when the intracellular concentration of LPS initiates pyroptosis. The mechanistic details remain to be elucidated, but the observations indicate that adipocytes are stimulated to cell death by processes that involve LPS from the gut microbiota. There is a complex interplay between the composition of the diet and microbiota. This influences the amount of LPS that is translocated from the gut. In particular, the lipid content of a meal may correlate with the amount of LPS built in to chylomicrons. [ABSTRACT FROM AUTHOR]

Ambient air pollution causes a range of adverse health effects, whereas effects of indoor sources of air pollution are not well described in high-income countries. We compared hazards of ambient air pollution and indoor sources with respect to important biomarkers of cardiorespiratory effects in terms of lung function and systemic inflammation in a middle-aged Danish cohort. Our cohort comprised 5199 men and women aged 49-63 years at the recruitment during April 2009 to March 2011, with information on exposure to second-hand smoke (SHS) and use of candles, wood stove, kerosene heater and gas cooker as well as relevant covariates. Ambient air pollution exposure was assessed as 2-year mean nitrogen dioxide (NO2) at the address (mean ± SD: 17.1 ± 9.9 μg/m3) and 4-day average levels of particulate matter with diameter <2.5 μm (PM2.5; mean ± SD: 12.5 ± 6.0 μg/m3) in urban background. Lung function was assessed as % predicted forced expiratory volume in the first second (FEV1) and inflammatory markers comprised interleukin-6 (IL-6), IL-10, IL-18, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hs-CRP). We used random-effect regression models controlling for potential confounders as well as models with further adjustment for self-reported health or for all other exposures. In models adjusted for confounders FEV1 was inversely associated with exposure to NO2, (-0,83% per 10 μg/m3; 95% CI: -1.26; -0.41%), SHS (-0.56% per 1 of 5 categories increment; 95% CI: -0.89; -0.23%), and gas cooker without hood (-0.89%; 95% CI: -1.62; -0.17%), whereas use of wood stove and candles showed positive associations, although these attenuated by mutual adjustment for all exposures or self-reported health. IL-6 showed positive associations with NO2 (6.30% increase in log-transformed values per 10 μg/m3; 95% CI: 3.54; 9.05%), PM2.5 (7.82% per 10 μg/m3; 95% CI: 3.35; 12.4%), SHS (4.38% per increase of 1 of 5 categories; 95% CI: 2.22; 6.54%) and use of kerosene (13.8%; 95% CI: 2.51; 25.1%), whereas the associations with use of wood stove and candles were inverse. PM2.5 and NO2 showed positive associations with IFN-γ and TNF-α, while PM2.5 further associated with IL-10 and IL-18. Hs-CRP was inversely associated with use of candles. These results suggest that the levels of exposure to ambient air pollution and SHS are more harmful than are the levels of exposure to indoor combustion sources from candles and wood stoves in a high-income setting. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to particulate matter (PM) may induce inflammation and oxidative stress in the airways. Carriers of null polymorphisms of glutathione S-transferases (GSTs), which detoxify reactive oxygen species, may be particularly susceptible to the effects of PM. Objectives: To investigate whether deletions of GSTM1 and GSTT1 modify the potential effects of exposure to indoor sources of PM on symptoms and objective markers of respiratory disease. Methods: We conducted a population-based, cross-sectional study of 3471 persons aged 18-69 years. Information about exposure to indoor sources of PM and respiratory symptoms was obtained by a self-administered questionnaire. In addition, measurements of lung function (spirometry) and fractional exhaled nitric oxide were performed. Copy number variation of GSTM1 and GSTT1 was determined by polymerase chain reaction-based assays. Results: We found that none of the symptoms and objective markers of respiratory disease were significantly associated with the GST null polymorphisms. An increasing number of positive alleles of the GSTM1 polymorphism tended to be associated lower prevalence of wheeze, cough, and high forced expiratory volume in 1 s (FEV1), but these trends were not statistically significant. Furthermore, we did not observe any statistically significant interactions between GST copy number variation and exposure to indoor sources of PM in relation to respiratory symptoms and markers. Conclusions: In this adult population, GST copy number variations were not significantly associated with respiratory outcomes and did not modify the effects of self-reported exposure to indoor sources of PM on respiratory outcomes. Please cite this paper as: Hersoug L-G, Brasch-Andersen C, Husemoen LLN, Sigsgaard T and Linneberg A. The relationship of glutathione-S-transferases copy number variation and indoor air pollution to symptoms and markers of respiratory disease. Clin Respir J 2012; 6: 175-185. [ABSTRACT FROM AUTHOR]

Background: Exposure to particulate matter (PM) outdoors can induce airway inflammation and exacerbation of asthma in adults. However, there is limited knowledge about the effects of exposure to indoor PM. The aim of this study was to investigate the association of exposure to indoor sources of PM with rhinitis symptoms, atopy and nitric oxide in exhaled air (FeNO) as a measure of airway inflammation. Methods: We conducted a population-based cross-sectional study of 3,471 persons aged 18-69 years. Exposure to indoor sources of PM and prevalence of rhinitis symptoms were assessed by a self-administered questionnaire. Atopy was defined as at least 1 positive test (≥0.35 kU/l) for serum-specific IgE against grass, birch, cat or Dermatophagoides pteronyssinus. Regression analyses were used to adjust for confounders. Results: Self-reported exposure to the use of woodstoves, candles or gas kitchen cookers was not significantly associated with either increased prevalence of rhinitis symptoms or atopy or increased levels of FeNO. The prevalence of atopy and allergic rhinitis and the levels of FeNO were significantly decreased among current and previous smokers. Exposure to environmental tobacco smoke (ETS) for 0.5-5 h, but not above 5 h, was significantly associated with a slightly increased prevalence of rhinitis symptoms. Conclusion: Self-reported exposure to the use of woodstoves, candles or gas cookers was not significantly associated with an increased risk of rhinitis symptoms or atopy, nor increased FeNO. Self-reported exposure to ETS was associated with a slightly higher prevalence of self-reported rhinitis symptoms without any clear dose-response relationship. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Exposure to particulate matter (PM) can induce airway inflammation and exacerbation of asthma. However, there is limited knowledge about the effects of exposure to indoor sources of PM. We investigated the associations between self-reported exposure to indoor sources of PM and lower airway symptoms and lung function. Methods: A population-based cross-sectional study of 3471 persons aged 18-69 years was conducted. Information about exposure to indoor sources of PM and airway symptoms was obtained from a self-administered questionnaire. Results: Exposure to wood stoves, candles and gas cookers was not significantly associated with an increased prevalence of lower respiratory symptoms or decreased lung function. In contrast, persons exposed to environmental tobacco smoke for >5 h/day had a significantly increased risk of 'wheeze' (OR 1.69, 95% CI: 1.24-2.30) and 'chronic cough' (OR 1.57, 95% CI: 1.12-2.20), as well as decreased lung function (FEV1% predicted), compared with those who were not exposed. Similar trends were observed in never smokers. Conclusions: In this cross-sectional study of an adult general population, self-reported exposure to environmental tobacco smoke, but not self-reported exposure to wood stoves, candles or gas cookers, appeared to be associated with an increased prevalence of lower airway symptoms and decreased lung function. [ABSTRACT FROM AUTHOR]

It has been proposed that exposure to infections and microbes protects against atopic diseases, but epidemiological data has so far been conflicting. We hypothesized that maternal exposure to infections and microbes before or during pregnancy would be of particular importance. To test this hypothesis, we studied the incidence of wheezing and atopic dermatitis (AD) in infants of mothers employed in child-care institutions – and thus presumably being highly exposed to infections and microbes – compared with infants of mothers not so employed. A total of 31471 mother-child pairs enroled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, maternal employment, and other variables were collected by interview at 12 and 30 wk of gestation, and 6 and 18 months of age, and by linkage to the Danish Medical Birth Register and the Child-care Database. The relative risk was estimated in Cox proportional hazard models. Analyses were stratified by sibling status (first born or not), as older siblings are likely to be a significant source of infectious agents. The adjusted relative risks of wheeze, recurrent wheeze and AD was 1.14 (95% CI: 0.96–1.37), 1.37 (95% CI: 1.05–1.77), and 1.03 (95% CI: 0.81–1.31), respectively, for first-born infants of mothers employed in child-care institutions compared with infants of mothers not so employed. There was no effect of maternal employment in child-care institutions among infants with older siblings. In conclusion, the results did not support the hypothesis that maternal microbial exposure before or during pregnancy as reflected by maternal employment in child-care institutions protects the offspring against infant wheeze and AD. [ABSTRACT FROM AUTHOR]

Background: There is evidence that chronic alcohol consumption impairs the T-helper 1 (Th1) lymphocyte-regulated cell-mediated immune response possibly favoring a Th2 deviation of the immune response. Moreover, a few epidemiological studies have linked alcohol consumption to allergen-specific IgE sensitization. Objective: To investigate the effects of alcohol consumption on the allergen-specific immune response in mice. Methods: BALB/cJBomTac mice were immunized intraperitoneally with ovalbumin (OVA) using a low dose sensitization protocol. Throughout the experiment, mice were kept on isocalorical liquid diets containing 0 to 6.2% ethanol. Evaluation of immunomodulatory effects of ethanol was based on measurements of total serum IgE, as well as OVA-specific IgE, IgG1, and IgG2a. Furthermore, levels of OVA-induced interleukin (IL)-4 and interferon- γ were determined in ex vivo splenocyte cultures. Results: Alcohol intake decreased the level of OVA-specific IgG2a in a dose-dependent manner, whereas high levels of alcohol markedly increased the level of total IgE, but not OVA-specific IgE. Th1 suppression was supported by the cytokine profile. Conclusions: Alcohol consumption induced a marked decrease in markers of the Th1-type allergen-specific immune response and an increase in total serum IgE. In this model, there was no effect of alcohol on OVA-specific IgE. Studies using other routes of immunization may be warranted. [ABSTRACT FROM AUTHOR]

Exposure to particles in the fine and ultrafine size range has been linked to induction of low-grade systemic inflammation, oxidative stress and development of cardiovascular diseases. Declining levels of endothelial progenitor cells within systemic circulation have likewise been linked to progression of cardiovascular diseases. The objective was to determine if exposure to fine and ultrafine particles from indoor and outdoor sources, assessed by personal and residential indoor monitoring, is associated with altered levels of endothelial progenitor cells, and whether such effects are related to leukocyte-mediated oxidative stress. The study utilized a cross sectional design performed in 58 study participants from a larger cohort. Levels of circulating endothelial progenitor cells, defined as either late (CD34 + KDR + cells) or early (CD34 + CD133 + KDR + cells) subsets were measured using polychromatic flow cytometry. We additionally measured production of reactive oxygen species in leukocyte subsets (lymphocytes, monocytes and granulocytes) by flow cytometry using intracellular 2′,7′-dichlorofluoroscein. The measurements encompassed both basal levels of reactive oxygen species production and capacity for reactive oxygen species production for each leukocyte subset. We found that the late endothelial progenitor subset was negatively associated with levels of ultrafine particles measured within the participant residences and with reactive oxygen species production capacity in lymphocytes. Additionally, the early endothelial progenitor cell levels were positively associated with a personalised measure of ultrafine particle exposure and negatively associated with both basal and capacity for reactive oxygen species production in lymphocytes and granulocytes, respectively. Our results indicate that exposure to fine and ultrafine particles derived from indoor sources may have adverse effects on human vascular health. [ABSTRACT FROM AUTHOR]

Exposure to ambient air particles is associated with elevated levels of DNA strand breaks (SBs) and endonuclease III, formamidopyrimidine DNA glycosylase (FPG) and oxoguanine DNA glycosylase-sensitive sites in cell cultures, animals and humans. In both animals and cell cultures, increases in SB and in oxidatively damaged DNA are seen after exposure to a range of engineered nanomaterials (ENMs), including carbon black, carbon nanotubes, fullerene C60, ZnO, silver and gold. Exposure to TiO2 has generated mixed data with regard to SB and oxidatively damaged DNA in cell cultures. Nanosilica does not seem to be associated with generation of FPG-sensitive sites in cell cultures, while large differences in SB generation between studies have been noted. Single-dose airway exposure to nanosized carbon black and multi-walled carbon nanotubes in animal models seems to be associated with elevated DNA damage levels in lung tissue in comparison to similar exposure toTiO2 and fullerene C60. Oral exposure has been associated with augmented DNA damage levels in cells of internal organs, although the doses have been typically very high. Intraveneous and intraperitoneal injection of ENMs have shown contradictory results dependent on the type of ENM and dose in each set of experiments. In conclusion, the exposure to both combustion-derived particles and ENMs is associated with increased levels of DNA damage in the comet assay. Particle size, composition and crystal structure of ENM are considered important determinants of toxicity, whereas their combined contributions to genotoxicity in the comet assay are yet to be thoroughly investigated. [ABSTRACT FROM AUTHOR]

Background Exposure to ambient air particulate matter (PM) has been linked to decline in pulmonary function and cardiovascular events possibly through inflammation. Little is known about individual exposure to ultrafine particles (UFP) inside and outside modern homes and associated health-related effects. Methods Associations between vascular and lung function, inflammation markers and exposure in terms of particle number concentration (PNC; d = 10-300 nm) were studied in a cross-sectional design with personal and home indoor monitoring in the Western Copenhagen Area, Denmark. During 48-h, PNC and PM2.5 were monitored in living rooms of 60 homes with 81 non-smoking subjects (30-75 years old), 59 of whom carried personal monitors both when at home and away from home. We measured lung function in terms of the FEV1/FVC ratio, microvascular function (MVF) and pulse amplitude by digital artery tonometry, blood pressure and biomarkers of inflammation including C-reactive protein, and leukocyte counts with subdivision in neutrophils, eosinophils, monocytes, and lymphocytes in blood. Results PNC from personal and stationary home monitoring showed weak correlation (r = 0.15, p = 0.24). Personal UFP exposure away from home was significantly inversely associated with MVF (1.3% decline per interquartile range, 95% confidence interval: 0.1-2.5%) and pulse amplitude and positively associated with leukocyte and neutrophil counts. The leukocyte and neutrophil counts were also positively and pulse amplitude negatively associated with total personal PNC. Indoor PNC and PM2.5 showed positive association with blood pressure and inverse association with eosinophil counts. Conclusions The inverse association between personal exposure away from home and MVF is consistent with adverse health effects of UFP from sources outside the home and might be related to increased inflammation indicated by leukocyte counts, whereas UFP from sources in the home could have less effect. [ABSTRACT FROM AUTHOR]

The development of products containing carbon nanotubes (CNTs) is a major achievement of nanotechnology, although concerns regarding risk of toxic effects linger if the hazards associated with these materials are not thoroughly investigated. Exposure to CNTs has been associated with depletion of antioxidants, increased intracellular production of reactive oxygen species and pro-inflammatory signaling in cultured cells with primary function in the immune system as well as epithelial, endothelial and stromal cells. Pre-treatment with antioxidants has been shown to attenuate these effects, indicating a dependency of oxidative stress on cellular responses to CNT exposure. CNT-mediated oxidative stress in cell cultures has been associated with elevated levels of lipid peroxidation products and oxidatively damaged DNA. Investigations of oxidative stress endpoints in animal studies have utilized pulmonary, gastrointestinal, intravenous and intraperitoneal exposure routes, documenting elevated levels of lipid peroxidation products and oxidatively damaged DNA nucleobases especially in the lungs and liver, which to some extent occur concomitantly with altered levels of components in the antioxidant defense system (glutathione, superoxide dismutase or catalase). CNTs are biopersistent high aspect ratio materials, and some are rigid with lengths that lead to frustrated phagocytosis and pleural accumulation. There is accumulating evidence showing that pulmonary exposure to CNTs is associated with fibrosis and neoplastic changes in the lungs, and cardiovascular disease. As oxidative stress and inflammation responses are implicated in the development of these diseases, converging lines of evidence indicate that exposure to CNTs is associated with increased risk of cardiopulmonary diseases through generation of a pro-inflammatory and pro-oxidant milieu in the lungs. [ABSTRACT FROM AUTHOR]