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Low-dose arsenic compromises the immune response to influenza A infection in vivo.

Kozul CD, Ely KH, Enelow RI, Hamilton JW - Environ. Health Perspect. (2009)

Bottom Line: Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection.We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA.

ABSTRACT

Background: Arsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week exposure to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components of the innate immune response in mouse lung, which we hypothesize is an important contributor to the increased risk of lung disease in exposed human populations.

Objectives: We investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease.

Methods: In this study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks, followed by intranasal inoculation with a sub lethal dose of influenza A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection.

Results: Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection. We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.

Conclusions: Our data indicate that chronic As exposure significantly compromises the immune response to infection. Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.

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Related in: MedlinePlus

Viral titers for flu on day 7 p.i. in mice exposed to control water or water containing 100 ppb As. Whole-lung homogenates were assessed for viral titers by the TCID50 method. See “Materials and Methods” for experimental details. Values shown are mean ± SEM from two experimental repeats (n= 3–6 per group).*p < 0.05 by two-tailed Student’s t-test.
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f2-ehp-117-1441: Viral titers for flu on day 7 p.i. in mice exposed to control water or water containing 100 ppb As. Whole-lung homogenates were assessed for viral titers by the TCID50 method. See “Materials and Methods” for experimental details. Values shown are mean ± SEM from two experimental repeats (n= 3–6 per group).*p < 0.05 by two-tailed Student’s t-test.

Mentions: Given that the inability to properly clear virus from the lung is positively correlated with increased risk of adverse outcomes, we examined the levels of influenza A virus in whole-lung homogenates using TCID50 determination at day 7 p.i. Relative to As-unexposed controls, the As-exposed mice exhibited a significant 10-fold increase in viral titers at this time point, correlating with their relative increase in morbidity (Figure 2).


Low-dose arsenic compromises the immune response to influenza A infection in vivo.

Kozul CD, Ely KH, Enelow RI, Hamilton JW - Environ. Health Perspect. (2009)

Viral titers for flu on day 7 p.i. in mice exposed to control water or water containing 100 ppb As. Whole-lung homogenates were assessed for viral titers by the TCID50 method. See “Materials and Methods” for experimental details. Values shown are mean ± SEM from two experimental repeats (n= 3–6 per group).*p < 0.05 by two-tailed Student’s t-test.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2737023&req=5

f2-ehp-117-1441: Viral titers for flu on day 7 p.i. in mice exposed to control water or water containing 100 ppb As. Whole-lung homogenates were assessed for viral titers by the TCID50 method. See “Materials and Methods” for experimental details. Values shown are mean ± SEM from two experimental repeats (n= 3–6 per group).*p < 0.05 by two-tailed Student’s t-test.
Mentions: Given that the inability to properly clear virus from the lung is positively correlated with increased risk of adverse outcomes, we examined the levels of influenza A virus in whole-lung homogenates using TCID50 determination at day 7 p.i. Relative to As-unexposed controls, the As-exposed mice exhibited a significant 10-fold increase in viral titers at this time point, correlating with their relative increase in morbidity (Figure 2).

Bottom Line: Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection.We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA.

ABSTRACT

Background: Arsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week exposure to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components of the innate immune response in mouse lung, which we hypothesize is an important contributor to the increased risk of lung disease in exposed human populations.

Objectives: We investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease.

Methods: In this study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks, followed by intranasal inoculation with a sub lethal dose of influenza A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection.

Results: Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection. We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.

Conclusions: Our data indicate that chronic As exposure significantly compromises the immune response to infection. Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.

Show MeSH
Related in: MedlinePlus