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Fetal Lead Exposure May Reduce Immunity

ITHACA, N.Y. -- Lead in the drinking water of pregnant rats causes long-term damage to the immune systems of their offspring, according to studies at the Cornell University Institute for Comparative and Environmental Toxicology.

If the finding also holds true for pregnant women exposed to lead, it could help explain why some babies are born with a lifelong predisposition to asthma and other allergies, as well as cancers, say Cornell scientists who report the discovery in the current issue of the journal Toxicological Sciences (Vol. 42, pp. 129-135).

"We found that low levels of lead in embryos -- levels that do not affect the mother's immune system -- produce serious long-term immune system defects as the young rats mature," says Rodney R. Dietert, professor of immunotoxicology in Cornell's College of Veterinary Medicine. "These are immune changes that could increase their risk for allergic disease while reducing their immunity to tumors."

The Cornell researchers are now conducting parallel studies on early lead exposure with embryonic chickens as animal models, but have no plans to extend the studies at the university to humans. But humans subjects, they say, would not be hard to find.

"Unfortunately, pregnant women even in this country are exposed to these levels of lead through drinking water, old paint and other sources," Dietert said. "And the situation is worse in developing countries, where leaded gasoline is still sold and women work in factories where lead is used."

Lead exposure is just one of the risk factors for immune-related disease now under consideration by epidemiologists in the United States. Among other possible risk factors is early exposure to airborne particles, such as those found in air polluted with diesel engine fumes.

Studies at the Cornell toxicology institute and the university's veterinary college used Fischer 334 rats, a standard animal model for human cancer studies. The pregnant rats were given drinking water containing lead acetate. The amount of lead was comparable, given the rats' lower body weight, to levels that humans might receive in water from old buildings with lead pipes and lead-based solder in pipe connections, and other sources.

The fetuses and newborn rats exposed to lead grew just as fast as those without lead exposure, the Cornell scientists reported.

But when they tested the rats at 13 weeks of age, the researchers found significant and potentially harmful alterations to immune systems of rats exposed to lead in the womb. In particular, the lead-exposed rats had an overabundance of type-2 helper T-cell activity compared to type-1 helper T-cell activity, diminished production of gamma interferon, depressed cell-mediated immune function, as well as elevated levels of nitric oxide tumor necrosis factor and IgE antibodies.

These are all indications, in the complex checks-and-balances realm of immunity, of a developing body that is ill-equipped to fend off infectious diseases and cancers while controlling the body's inclination to injure itself in allergic and autoimmune diseases. "Exposure to lead at these levels is not the kind of assault that can destroy the kidneys in 24 hours," Dietert says. "These exposures take time to play out, but ultimately they can be just as problematic relative to quality of life."

Writing in the toxicology journal, the Cornell researchers concluded: "Based on these results, if there are key periods of early immune development which are particularly susceptible to persistent lead-induced alterations, it is possible that even short-term exposure of pregnant females, in rodents or in other species including humans, could compromise offspring immune function."

Ongoing work in the project is focusing on a likely "window of susceptibility" during development, when the immune system is assembling its defenses and disruption by lead could produce persistent damage to immune defenses.

In addition to Dietert, the lead studies were conducted by Capt. Thomas E. Miller, USAF, a Cornell graduate student at the time of the experiments; Karen A. Golemboski, senior research associate; Richard S. Ha, graduate student at the time; Terry Bunn, graduate student; and Forrest S. Sanders, technician in veterinary microbiology and immunology.

The study was funded by the National Institute of Environmental Health Sciences' Superfund Basic Research and Education Program and administered through the U.S. Environmental Protection Administration.

Source: Cornell University News Service . May 1998.

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