Re: Arsenic - A Fatal Complication for Pandemic Flu - MUST READ
http://www.environmentalhealthnews.org/ehs/newscience/low-dose-arsenic-alters-mouse-response-to-flu
Arsenic makes mice more susceptible to H1N1 flu virus.
Jul 17, 2009
Kozul, CD, KH Ely, RI Enelow and JW Hamilton. 2009. Low dose arsenic compromises the immune response to influenza A infection in vivo. Environmental Health Perspectives doi:10.1289/ehp.0900911.
Context
What did they do?
What did they find?
What does it mean?
Resources
More new science from EHN
Synopsis by Kathleen M. McCarty, Sc.D. and Wendy Hessler
2009-0713womanatwellbrazil
World Bank
People around the world drink well water that is tainted with arsenic.
Low dose exposure to arsenic compromises the immune response to infection in mice, increasing their vulnerability to the flu virus. By itself, the metal altered the number and function of certain immune cells. The changes predisposed the rodents to more severe reactions when exposed to the Influenza A virus.
This is the first study to link arsenic exposure to a reduced immune response. The results suggest those people most exposed to arsenic through their drinking water may be more susceptible to illness and possibly death when infected with the H1N1 swine flu virus.
Context
Arsenic is a natural metal found globally. It occurs in higher levels and is more widespread in some areas of the world – such as Bangladesh, other Southeast Asian countries and Mexico – than other areas – such as the US – due to regional geology.
People are exposed to arsenic mainly through drinking water from underground wells (Kumar et al. 2009). It leaches naturally into the water from deposits in the bedrock or from areas disturbed by human activity – for example, mining or drilling.
When arsenic is in its inorganic form, it is a human carcinogen and has been linked to liver, bladder, kidney and lung cancers (Marshal et al. 2007). Arsenic is also associated with increased risk of type II diabetes, heart and circulation problems, lung disfunctions and compromised immune system function. It is unique because it can affect lung health after eating rather than breathing. The organic form of arsenic, present in some seafood, is not associated with these health outcomes and is not a threat to human health.
The risk to human health depends on many factors, including dose and length of exposure. Public water supplies are monitored for the metal. The drinking water standard in the US and by the World Health Organization (WHO) is 10 parts per billion (ppb) of arsenic.
Yet, millions of people worldwide are exposed to much higher levels on a regular basis. And, cell and animal studies show some effects below that standard (Kozul et al. 2009).
H1N1 flu virus is a human flu that was first observed in April 2009. Government health organizations consider the strain highly virulant and one that could cause a worldwide flu epidemic (H1N1 also called the swine flu).
It is estimated that a half million people worldwide die each year because of influenza. Lung and other respiratory infections sometime accompany the flu and increase the risk of death. Recent research has hinted that environmental contaminants, such as dioxin and cigarette smoke, could affect the immune response in people and make them more susceptible to infections and illnesses (Burleson et
al. 1996; Gualano et al. 2008; Warren et al. 2000)
The immune system is a complex network of organs and cells that are designed to attack and destroy foreign invaders, such as bacteria and viruses. Dendrite cells are important players in that process because they help start the immune response by activating the T cells that latch onto and try to destroy the pathogens.
What did they do?
Mice were separated into four groups – arsenic exposed, flu exposed, arsenic plus flu exposed, no exposure (controls) – to determine if arsenic alters the immune response to lung infection in mice.
The researchers exposed some of the rodents to a chronic, low dose of arsenic (100 ppb) in drinking water for five weeks. The mice were then injected with the H1N1 virus, and their responses were compared with the other three groups for their ability to deal with the infection.
The mice were weighed daily and were considered very ill if they lost more than 20 percent of their body weight. A number of immune system functions were measured in the animals, including the number of infected lung cells and the levels of cytokines, chemokines, albumin and dendritic cells.
What did they find?
Arsenic exposure by itself and in combinations with the flu virus was associated with a number of significant changes in the rodents' immune system and in their response to influenza.
The mice exposed to both arsenic and the virus had a much greater risk of severe disease than mice exposed only to arsenic or only to the H1N1 virus. The co-exposed animals lost a great deal of weight (more than 20 percent) and were so sick they were euthanized.
The co-exposed mice, when compared to mice exposed to only the flu virus, had a 10-fold increase in lung influenza virus antibodies that occurred about the same time they got severely ill, about day 7 after being infected. The lungs started to fill with water and hemorrhaged. They also had fewer dendritic cells in the lymph nodes at the beginning of the flu infection.
The mice exposed only to the flu virus lost some weight but recovered and were well again after 16 days.
Alone, arsenic affected neither weight nor growth in the mice, but it did affect the immune response relative to the control animals. The exposure changed some important immune cell functions, reducing dendridic cell movement into the lungs and decreasing both macrophage and neutrophil numbers and percents of cells. These changes predisposed the mice to the severe immune failure following H1N1 infection.
"Thus, the increased morbidity was due to the combination of arsenic in drinking water and influenza infection at an infectious dose at which mice not exposed to arsenic recover," explain the authors.
What does it mean?
Low-dose arsenic exposure had a dramatic effect on immune system responses which results in a more acute sickness to the H1N1 flu virus.
This is the first time arsenic exposure is shown to affect the immune system and the dendritic cells that lead the immune system response against infections. While this study was conducted in mice, it suggests a potential role for arsenic to modify exposure to H1N1 flu virus and immune response in humans.
Human population studies have reported that arsenic exposure through drinking water increases the risk of several respiratory diseases, including lung cancer, lung function and bronchiectasis. This mouse study provides a description of how arsenic may influence the severity of these diseases and raises new study questions. Furthermore, the results of this study support that health effects can be observed with low dose inorganic arsenic exposure.
These findings have global implications. Inorganic arsenic exposure through drinking water is a serious concern in Bangladesh, India, Argentina, Mexico, Vietnam, Chile and other regions. Worldwide there are millions of individuals with drinking water concentrations between 50 and 1,500 ppb.
These same regions, often in southeast Asia, Mexico and parts of South America, are also regions with high rates of viral outbreaks of various flu strains. This study used the H1N1 flu virus, which is the same virus responsible for the recent pandemic.
Public water supplies are tested for arsenic concentration, and there are standards in place. While the US drinking water standard is 10 ppb, this standard does not cover private wells. Wells in New Hampshire, Nevada and other regions of the US are reported to have concentrations similar to those used in this study.
Between 5-20 percent of the world's population will contract influenza infection annually. Infection with the flu virus results in more than 3-5 million hospitalizations and between 250,000 and 500,000 deaths worldwide. In the US, there are 200,000 cases of hospitalization due to influenza infection and an estimated 35,000 deaths (not H1N1-related).
The authors conclude that identifying risk factors, including environmental exposures such as arsenic, could have an immediate impact on protecting public health.
Resources
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Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on influenza virus host resistance
in mice. Fundamental and Applied Toxicology 29(1):40-47.
Gever, J. Arsenic in drinking water linked to Type 2 Diabetes. MedPage Today August 19, 2008.
Gualano, RC, MJ Hansen, R Vlahos, JE Jones, RA Park-Jones, G Deliyannis, SJ Turner, KA Duca and GP Anderson. 2008.
Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection
in mice. Respiratory Research 9:53.
H1N1 flu. Centers for Disease Control and
Kozul, CD, TH Hampton, JC Davey, JA Gosse, AP Nomikos, P Eisenhauer, DJ Weiss, JE Thorpe, MA Ihnat and JW Hamilton. 2009.
Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung. Environmental Health Perspectives 117:1108–1115.
Kumar, A, P Adak, PL Gurian and JR Lockwood. 2009. Arsenic exposure in US public and domestic drinking water supplies: A comparative risk assessment. Journal of Exposure Science and Environmental Epidemiology doi:10.1038/jes.2009.24.
Marshall, G, C Ferreccio, Y Yuan, MN Bates, C Steinmaus, S Selvin, J Liaw and AH Smith. 2007. Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. Journal of the National Cancer Institute 99(12):920-8.
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Warren, TK, KA Mitchell, and BP Lawrence. 2000. Exposure to 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) suppresses the humoral and cell-mediated immune responses to influenza
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