Arsenic makes mice more susceptible to H1N1 flu virus.

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.