Low Level Mercury Exposure Accelerates Lupus in Mice

BALTIMORE, Maryland, September 4, 2003 (ENS) - Exposure to low levels of mercury can speed up and worsen the symptoms of an autoimmune disease in mice, even when the exposure occurs before the development of the disease, according to new research published by the National Institute of Environmental Health Sciences, a government agency.

The study conducted at the University of Maryland School of Medicine is the first to connect low level mercury exposure to the severity of the autoimmune disease lupus in mice after they develop the disease.

Lupus is a chronic disease that causes inflammation of connective tissue. The most common form of lupus affects exposed areas of the skin, while the more serious and potentially fatal form can affect many systems of the body including the kidneys. It is an autoimmune disorder, in which the immune system for unknown reasons, attacks connective tissue as though it were foreign.


Systemic lupus erythematosis rash on the face (Photo courtesy National Institutes of Health)
The lead investigator of the study, Charles S. Via, M.D., professor of medicine, microbiology and immunology at the University of Maryland School of Medicine, says previous studies have found that mercury exposure in animals can worsen pre-existing autoimmune disease and even induce autoimmune disease in susceptible animals.

"Our study takes the link further by demonstrating that exposure to mercury prior to the induction of an autoimmune disease in mice significantly worsens the severity of that disease after it develops," says Dr. Via, who is also a rheumatologist at the University of Maryland Medical Center.

In this study, healthy mice that were not genetically susceptible to mercury induced autoimmune disease were given injections of low dose inorganic mercury over the course of two weeks.

The levels of mercury and the length of exposure chosen were much lower than the range commonly used in mouse studies of mercury toxicity.

Five days later, the mice were given cells from a lupus inclined mouse strain to induce lupus-like chronic graft-versus-host disease, a well established mouse model of acquired autoimmunity.

Dr. Via says the results obtained by his research team were a surprise to him.

Mercury exposure accelerated the deaths of the lupus-induced mice and sped up the course of a kidney disease associated with lupus. Further, antibodies, or markers characteristic of lupus-like autoimmunity were significantly elevated in the mice that had been pretreated with mercury.

"Our findings suggest that low level mercury exposure does not cause lupus," says Dr. Via. "Lupus is clearly multifactorial. You have to have a susceptible individual who has the appropriate environmental exposure. But our study clearly shows that mercury can act as a disease modifier for lupus. Exposure to mercury might either lower the threshold of susceptibility, or increase the severity of the disease."

Exposure to mercury occurs from breathing contaminated air, ingesting contaminated water and food, and having dental and medical treatments, according to the federal Agency for Toxic Substances and Disease Registry (ATSDR).

People can be exposed by breathing mercury vapors in air from spills, incinerators, and industries that burn mercury containing fuels.


Woman showing symptoms of systemic lupus erythematosus (Photo courtesy Indiana University School of Medicine)
Eating fish or shellfish contaminated with methylmercury increases human exposure and so does the release of mercury from dental work and medical treatments, the ATSDR says.

Breathing contaminated workplace air or skin contact during use in dental, health services, chemical, and other industries that use mercury also increases exposure.

Mercury, at high levels, may damage the brain, kidneys, and developing fetus, the ATSDR warns. This chemical has been found in at least 714 of 1,467 Superfund sites identified by the Environmental Protection Agency.

Lupus can be a killer. A study released in May 2002 by the Centers for Disease Control showed that systemic lupus erythematosus, a chronic and potentially life threatening disease, caused 22,861 deaths from from 1979 to 1998. About one-third of the deaths occurred among persons under 45 years old.

Black women aged 45 to 64 years had the highest death rate and biggest increase in death rates - nearly 70 percent - over the 20 years studied.

"There is considerable concern over potential neurotoxic effects associated with current levels of human exposure to mercury," says study co-author, Ellen Silbergeld, Ph.D., a professor of Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health, who formerly worked at the University of Maryland School of Medicine.

"These results suggest that we should examine the immune system as a target of mercury toxicity in humans," Silbergeld said.

Dr. Via says the researchers have begun additional studies to determine whether subtle abnormalities remain after mercury clears from the body that may produce the modifications in lupus.

"We can speculate about a lot of possible mechanisms, but we clearly need further study to determine exactly how mercury accelerates lupus," says Dr. Via.

Their study appears in the August edition of the journal "Environmental Health Perspectives," published by the National Institute of Environmental Health Sciences, part of the National Institutes of Health.