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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

Morbidity of influenza infection (measured by weight loss) in mice exposed to control water or water containing 100 ppb As. One experiment was conducted for days 0–16 (n = 6–8 per group), and three additional experimental repeats were conducted for days 0–7 (n = 6 per group per experiment). See “Materials and Methods” for experimental details. Values shown are mean ± SEM. The p-value for overall significance between groups exposed to flu alone or As + flu is p < 0.0001 (two-way ANOVA).**p < 0.01, and #p < 0.001, for individual time point exposures.
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f1-ehp-117-1441: Morbidity of influenza infection (measured by weight loss) in mice exposed to control water or water containing 100 ppb As. One experiment was conducted for days 0–16 (n = 6–8 per group), and three additional experimental repeats were conducted for days 0–7 (n = 6 per group per experiment). See “Materials and Methods” for experimental details. Values shown are mean ± SEM. The p-value for overall significance between groups exposed to flu alone or As + flu is p < 0.0001 (two-way ANOVA).**p < 0.01, and #p < 0.001, for individual time point exposures.

Mentions: As shown in Figure 1, after a 5-week exposure to 100 ppb As in drinking water, mice infected with influenza A (H1N1) displayed a significant increase in morbidity. By day 8 postinfection (p.i.), the As-exposed mice displayed such severe morbidity (e.g., body weight decrease ≥ 20%) that those experimental groups were euthanized in compliance with institutional IACUC standards. Because of the severity of these responses, subsequent analyses focused on day 3 and day 7 p.i. In contrast, a parallel group of control mice infected with influenza but not exposed to As displayed a moderate weight loss, but then began to recover weight by day 10 p.i., with complete weight recovery by day 16 p.i. (Figure 1). Exposure to As alone in the absence of viral infection did not influence weight or growth over the 5-week period, nor did anesthesia alone, with or without respiratory exposure vehicle, in either the control or As-exposed mice (data not shown). Thus, the increased morbidity was due to the combination of As in drinking water and influenza infection at an infectious dose at which mice not exposed to As recover.


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)

Morbidity of influenza infection (measured by weight loss) in mice exposed to control water or water containing 100 ppb As. One experiment was conducted for days 0–16 (n = 6–8 per group), and three additional experimental repeats were conducted for days 0–7 (n = 6 per group per experiment). See “Materials and Methods” for experimental details. Values shown are mean ± SEM. The p-value for overall significance between groups exposed to flu alone or As + flu is p < 0.0001 (two-way ANOVA).**p < 0.01, and #p < 0.001, for individual time point exposures.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f1-ehp-117-1441: Morbidity of influenza infection (measured by weight loss) in mice exposed to control water or water containing 100 ppb As. One experiment was conducted for days 0–16 (n = 6–8 per group), and three additional experimental repeats were conducted for days 0–7 (n = 6 per group per experiment). See “Materials and Methods” for experimental details. Values shown are mean ± SEM. The p-value for overall significance between groups exposed to flu alone or As + flu is p < 0.0001 (two-way ANOVA).**p < 0.01, and #p < 0.001, for individual time point exposures.
Mentions: As shown in Figure 1, after a 5-week exposure to 100 ppb As in drinking water, mice infected with influenza A (H1N1) displayed a significant increase in morbidity. By day 8 postinfection (p.i.), the As-exposed mice displayed such severe morbidity (e.g., body weight decrease ≥ 20%) that those experimental groups were euthanized in compliance with institutional IACUC standards. Because of the severity of these responses, subsequent analyses focused on day 3 and day 7 p.i. In contrast, a parallel group of control mice infected with influenza but not exposed to As displayed a moderate weight loss, but then began to recover weight by day 10 p.i., with complete weight recovery by day 16 p.i. (Figure 1). Exposure to As alone in the absence of viral infection did not influence weight or growth over the 5-week period, nor did anesthesia alone, with or without respiratory exposure vehicle, in either the control or As-exposed mice (data not shown). Thus, the increased morbidity was due to the combination of As in drinking water and influenza infection at an infectious dose at which mice not exposed to As recover.

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