Lead may foster immune attack on brain.

High exposures to lead, a toxic heavy metal, have been linked to a range of neurological problems, including reduced IQ, impaired hearing, and trouble maintaining motor control and balance. Science has yet to tease out what lead does to the brain to yield such effects, but it now appears that this metal may eventually enlist the body's immune system in its attacks.

Because the immune system doesn't tend to operate in the brain and brain proteins don't ordinarily enter the blood or the rest of the body, the system's sentry molecules will treat any brain protein they encounter as a foreign invader -- and develop antibodies to it. These antibodies, therefore, indirectly signal the existence of brain damage.

Over the past 2 years, Hassan A.N. El-Fawal at New York University's Institute of Environmental Medicine in Tuxedo, N.Y., has correlated brain proteins circulating in the blood of lead-exposed rodents with bloodborne antibodies to them. If he and his colleagues could link lead exposure to these antibodies, they would have a simple blood test to pick up even early effects of this metal on the brain -- changes that predate overt symptoms and irreversible damage.

They're not there yet. However, their studies have uncovered evidence not only that lead toxicity leaves a telltale trail of brain proteins in the blood, but also that lead enhances the responsiveness of the immune system in attacking those proteins.

Working with El-Fawal and Carroll A. Snyder, Stacey J. Waterman recently inoculated healthy mice with three doses of either of two brain proteins; the doses were delivered 2 weeks apart. Some animals received normal, healthy forms of the proteins, while others got versions that had been incubated for 24 hours with lead.

In the December Environmental Health Perspectives, these NYU researchers now report that when assayed 10 days after the last dose, all mice showed some antibodies to the brain proteins in their blood. But those that had received lead-incubated proteins exhibited significantly more. These data show that "lead enhances the immunogenicity of two nervous system proteins," the team concludes, and supports the hypothesis that lead's neurotoxicity traces to "production of autoantibodies against neural proteins."

In a related, unpublished study, El-Fawal correlates the concentration of these antibodies in the blood of Egyptian battery workers to their lead exposure -- and to the severity of their neurological symptoms.

Though preliminary, the NYU group's research "is very suggestive" that antibodies to brain proteins might be "setting up an immunological attack on the brain," notes David A. Lawrence of New York State's Wadsworth Center in Albany. His own work indicates that exposure to lead and various other heavy metals can upset the balance between two classes of the immune system's helper T cells in favor of cells less able to ward off certain viral infections.

While promising, El-Fawal's goal of establishing neuroantibodies as markers of lead's neurotoxicity won't prove easy, observes neuroscientist James O'Callaghan, who is working at Rockefeller University in New York City.

Indeed, adds George Leikauf of the University of Cincinnati, while the doubling and tripling of antibody concentrations observed after exposure to lead-incubated proteins "are statistically significant, physiologically they're not." However, El-Fawal counters, neuroantibody amounts he's seen in lead-exposed workers are typically 1,000 times greater than those in nonexposed individuals.