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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

Effect of chronic exposure to As (100 ppb) in drinking water for 5 weeks followed by inoculation with influenza A. (A, B ) Gross histology of representative lungs from mice given control drinking water (Flu alone; A) and As in drinking water (Flu + As; B) at day 7 p.i. after lungs were perfused with PBS and inflated. (C ) BALF assessed for albumin by ELISA on day 0 and day 3 and day 7 p.i. (D ) Oxygen saturations measured with the MouseOx system at day 0 and day 7 p.i. In B and C, values are mean ± SEM from one representative experiment (n= 6 per group).**p < 0.01, and #p < 0.001, by two-tailed Student’s t-test.
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f3-ehp-117-1441: Effect of chronic exposure to As (100 ppb) in drinking water for 5 weeks followed by inoculation with influenza A. (A, B ) Gross histology of representative lungs from mice given control drinking water (Flu alone; A) and As in drinking water (Flu + As; B) at day 7 p.i. after lungs were perfused with PBS and inflated. (C ) BALF assessed for albumin by ELISA on day 0 and day 3 and day 7 p.i. (D ) Oxygen saturations measured with the MouseOx system at day 0 and day 7 p.i. In B and C, values are mean ± SEM from one representative experiment (n= 6 per group).**p < 0.01, and #p < 0.001, by two-tailed Student’s t-test.

Mentions: At day 7 p.i., obvious gross histologic changes in the As-exposed mice, including edema and hemorrhaging, could be observed by visual inspection of the whole lung (Figure 3A,B). We measured capillary leakage into the lungs by assaying albumin concentrations in the BALF. Albumin concentrations were significantly increased in the As-exposed versus unexposed mice at day 7 p.i. Albumin concentrations did not differ between control or As-exposed mice before infection or at day 3 p.i. (Figure 3C). Because an increased severity of influenza infection often correlates with a decrease in SpO2, we measured the oxygen saturation levels in infected control and As-exposed conscious mice at day 7 p.i. The As-exposed mice displayed a significant decrease in SpO2 levels compared with control mice (Figure 3D). The average SpO2 reading for the control mice infected with influenza was 95.2% (range, 93–97.5%), and the average SpO2 reading for As-exposed mice infected with influenza was 82.9% (range, 75–90%). Three of the six As-exposed mice had SpO2 readings considered to be dangerously low (i.e., ≤ 80%). Exposure to As in the absence of infection had no effect on peripheral oxygen saturation levels.


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)

Effect of chronic exposure to As (100 ppb) in drinking water for 5 weeks followed by inoculation with influenza A. (A, B ) Gross histology of representative lungs from mice given control drinking water (Flu alone; A) and As in drinking water (Flu + As; B) at day 7 p.i. after lungs were perfused with PBS and inflated. (C ) BALF assessed for albumin by ELISA on day 0 and day 3 and day 7 p.i. (D ) Oxygen saturations measured with the MouseOx system at day 0 and day 7 p.i. In B and C, values are mean ± SEM from one representative experiment (n= 6 per group).**p < 0.01, and #p < 0.001, 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

f3-ehp-117-1441: Effect of chronic exposure to As (100 ppb) in drinking water for 5 weeks followed by inoculation with influenza A. (A, B ) Gross histology of representative lungs from mice given control drinking water (Flu alone; A) and As in drinking water (Flu + As; B) at day 7 p.i. after lungs were perfused with PBS and inflated. (C ) BALF assessed for albumin by ELISA on day 0 and day 3 and day 7 p.i. (D ) Oxygen saturations measured with the MouseOx system at day 0 and day 7 p.i. In B and C, values are mean ± SEM from one representative experiment (n= 6 per group).**p < 0.01, and #p < 0.001, by two-tailed Student’s t-test.
Mentions: At day 7 p.i., obvious gross histologic changes in the As-exposed mice, including edema and hemorrhaging, could be observed by visual inspection of the whole lung (Figure 3A,B). We measured capillary leakage into the lungs by assaying albumin concentrations in the BALF. Albumin concentrations were significantly increased in the As-exposed versus unexposed mice at day 7 p.i. Albumin concentrations did not differ between control or As-exposed mice before infection or at day 3 p.i. (Figure 3C). Because an increased severity of influenza infection often correlates with a decrease in SpO2, we measured the oxygen saturation levels in infected control and As-exposed conscious mice at day 7 p.i. The As-exposed mice displayed a significant decrease in SpO2 levels compared with control mice (Figure 3D). The average SpO2 reading for the control mice infected with influenza was 95.2% (range, 93–97.5%), and the average SpO2 reading for As-exposed mice infected with influenza was 82.9% (range, 75–90%). Three of the six As-exposed mice had SpO2 readings considered to be dangerously low (i.e., ≤ 80%). Exposure to As in the absence of infection had no effect on peripheral oxygen saturation levels.

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