Murine studies suggest that exposure to phthalates-a group of chemicals used in the production of household and consumer products, including plastics-may increase susceptibility to systemic lupus erythematosus (SLE) and possibly other autoimmune disorders. The new findings appear in the August issue of the Journal of Autoimmunity.¹

The incidence of autoimmune disorders such as SLE is on the rise, and there is a high level of interest in understanding how genetic predisposition, as well as hormonal and environmental factors, contributes to the development of such disorders.

Mouse antibodies against phthalates are nearly identical to certain anti-DNA antibodies, according to lead author Swapan K. Ghosh, PhD, professor and interim chair of life sciences at Indiana State University in Terre Haute, Indiana. Specifically, "the light chain of antibody to phthalate is 98% the same as the anti-self antibody found in mouse lupus that is associated with the anti-DNA monoclonal antibody, BV-04. In contrast, the heavy chain is 70% homologous," Dr. Ghosh tells CIAOMed. Given the mechanism, he thinks it is possible that phthalates may aggravate many different autoimmune disorders.

"Our findings clearly show that lupus can be caused by an environmental factor like phthalate, which is present in toys, and many other plastic products, including PVC pipes and medical devices, and in beauty products," he says.

Genetic susceptibility to environmental factor is key

To arrive at their findings, Dr. Ghosh and his colleague So-Yon Lim, PhD, now a post-doctoral researcher at Harvard University Medical School in Boston, Massachusetts, injected BALB/c, NZB/W F1, and two other strains of mice with phthalate isomers and found that the injections triggered lupus, caused glomerulonephritis, and considerably shortened the lifespan of mice with a genetic disposition to the disease. "Not everyone who is exposed to phthalate becomes susceptible to lupus-like disorder, because we know from these studies that there is a genetic propensity in some mouse strains and not in others," Dr. Ghosh tells CIAOMed.

Only the lupus-prone NZB/W F1 mice suffered from kidney failure and high mortality, the study found. By contrast, the BALB/c mice developed idiotype-specific CD8+ suppressor T cells, which downregulated autoreactive B cells and effectively blocked the antiphthalate antibodies.

But, Dr. Ghosh cautions, "There is no direct human link yet, so we don't want to scare anybody." The next step in the research is to try to establish the human link.

Some physicians skeptical of the impact on humans

Some physicians are highly skeptical of drawing any conclusions about phthalates and autoimmunity from this study.

"Rat experiments are not applicable to human beings, period," says Gilbert Ross, MD, medical and executive director of the American Council on Science and Health in New York City. "The doses of toxins administered to rats in these studies are many orders of magnitude higher than humans have to levels of exposure in the environment, including cosmetics and flexible medical devices," Dr. Ross tells CIAOMed. "We should not be overly concerned about cosmetics and flexible medical devices being major causes of systemic lupus erythematosus," he says.

Reference:

Lim S-Y, Ghosh SK. Autoreactive responses to environmental factors: 3. Mouse strain-specific differences in induction and regulation of anti-DNA antibody responses due to phthalate-isomers. J Autoimmun. 2005;25:33-45.