Immune abuse: methamphetamine is linked to cardiac damage.

Use of the drug methamphetamine can drastically alter the array of immune proteins unleashed in the body, a study of rats shows. The finding may explain some cardiac problems seen in longtime methamphetamine abusers.

Methamphetamine is an inexpensive drug made illegally in home laboratories. It's a strong stimulant that can lead to brain damage.

Methamphetamine use also leads to a racing heartbeat and high blood pressure, which may result in chronic strain and heart injury.

In addition, the drug may cause inflammation in heart arteries, says study coauthor Tobin J. Dickerson, a biochemist at the Scripps Research Institute in La Jolla, Calif.

In earlier work, he and his colleagues had found that methamphetamine binds to proteins in the body, using glucose as glue. The result is what's called a glycated protein. When the scientists injected rodents with methamphetamine-glycated proteins, they found that the animals made antibodies against the aberrant proteins as if they were foreign bodies.

Dickerson and his colleagues hypothesize that this immune response is part of a destructive inflammatory reaction triggered when glycated proteins form deposits in blood vessels.

In the new study, the scientists analyzed this process in rats that were able to self-administer methamphetamine at various times during a 3-month period. The researchers surgically implanted intravenous lines into the backs of 27 laboratory rats. Whenever a rat pressed a lever in its cage, the line delivered a small dose of methamphetamine or an inert substance to the animal's circulatory system. The drug was available for 6 hours a day for some rats and 1 hour a day for others. A control group of rats received the placebo infusions.

The animals getting the drug soon sensed its stimulatory effects. "The 6-hour rats were pressing the lever pretty often" says Dickerson. These animals formed five times as many antibodies against the glycated proteins as did rats not getting the drug, the researchers report in an upcoming Proceedings of the National Academy of Sciences. Rats with less access to methamphetamine made half as many antibodies as the more heavily exposed rats did. Other tests showed that the rats that had access 6 hours a day had higher concentrations of inflammatory proteins in their blood than did rats in either of the other two groups.

"We think the glycated proteins bind to cells along blood vessel walls, and then antibodies bind to them," Dickerson says. Such binding would attract a flood of inflammatory immune cells that in normal circumstances would be attacking pathogens. "In this case, they attack your own blood vessels," he says. "This is a chronic-damage scenario."

Previous research suggested a link between methamphetamine and aberrant immunity, says Timothy W. Lineberry, a psychiatrist at the Mayo Clinic College of Medicine in Rochester, Minn. "This provides a more complete understanding of the possible mechanisms that underlie chronic [methamphetamine] problems."

Immunologist Ronald R. Watson of the University of Arizona in Tucson says that his team has done work suggesting that methamphetamine damages the heart by weakening collagen, a protein that forms part of the heart's structure. The new study offers "an alternative explanation," he says, acknowledging that both theories might prove valid.