This colorized negative stained transmission electron micrograph (TEM) depicts some of the ultrastructural morphology of the A/CA/4/09 swine flu virus.
The ability to mount an immune response to influenza A (H1N1) infection is significantly compromised by a low level of arsenic exposure that commonly occurs through drinking contaminated well water, scientists at the Marine Biological Laboratory (MBL) and
Joshua Hamilton, the MBL's chief academic and scientific officer and a senior scientist in the MBL's
"When a normal person or mouse is infected with the flu, they immediately develop an immune response," says
Respiratory infections with influenza A virus are a worldwide health concern and are responsible for 36,000 deaths annually. The recent outbreak of the influenza A H1N1 substrain ("swine flu") -- which is the same virus that Hamilton and his colleagues used in their arsenic study -- to date has killed 72 people in Mexico and six in the United States.
"One thing that did strike us, when we heard about the recent H1N1 outbreak, is
The U.S. Environmental Protection Agency considers 10 ppb arsenic in drinking water "safe," yet concentrations of 100 ppb and higher are commonly found in well water in regions where arsenic is geologically abundant, including upper New England (
Arsenic does not accumulate in the body over a lifetime, as do other toxic metals such as lead, cadmium, and mercury. "Arsenic goes right through us like table salt," Hamilton says. "We believe for arsenic to have health consequences, it requires exposure day after day, year after year, such as through drinking water."
Arsenic exposure not only disrupts the innate immune system, as the present study shows, it also disrupts the endocrine (hormonal) system in an unusually broad way, which Hamilton's laboratory discovered and first reported in 1998.
"Most chemicals that disrupt hormone pathways target just one, such as the estrogen pathway," he says. "But arsenic disrupts the pathways of all five steroid hormone receptors (estrogen, testosterone, progesterone, glucocorticoids, and mineralocorticoids), as well as several other hormone pathways. You can imagine that just this one effect could play a role in cancer, diabetes, heart disease, reproductive and developmental disorders–all the diseases that have a strong hormonal component."
At this point, Hamilton thinks arsenic disrupts the innate immune system and the endocrine system through different mechanisms. "Arsenic may ultimately be doing a similar thing inside the cell to make these effects happen, but the targets are likely different," he says. The proteins that mediate hormone response are different than the proteins that mediate the immune response. "We don't yet know how arsenic disrupts either system at the molecular level. But once we know how it affects one system, we will have a pretty good idea of how it affects the other systems as well."
Presently, Hamilton's lab is focused on understanding the unusual "biphasic" effect that arsenic has on the endocrine system. At very low doses, arsenic stimulates or enhances hormone responses, while at slightly higher doses (still within the range found in drinking water), it suppresses these same hormone responses.
"Why we see that dramatic shift (from hormone enhancement to suppression) over such a narrow dose range is quite fascinating and totally unknown," Hamilton says. "Our principal focus is to figure out this switch. We think that will help us understand why arsenic does what it does in the body."
This research was funded by the Dartmouth Toxic Metals Research Program Project by a grant from NIH-NIEHS and its Superfund Basic Research Program (grant P42 ES007373).
Reference: Kozul, C.D., Ely, K.H., Enelow, R.I., and Hamilton, J.W. (2009) Low dose arsenic compromises the immune response to influenza infection in vivo. Environ Health Perspec.