Misoprostol, a companion drug to RU-486 that is used during medication abortions, is safe when taken orally but could reduce the body’s immune response when used vaginally, according to a study released Monday by researchers at the University of Michigan.

Vaginal use of the drug may be responsible for the deaths by rare infection of eight women since 2000, the study’s authors said.

Misoprostol is approved by the U.S. Food and Drug Administration to be taken orally along with RU-486 to end an early-term pregnancy. RU-486 stops the pregnancy, while misoprostol allows the uterus to contract and the cervix to dilate so that a woman will expel the embryo. More than a half-million women in the United States have used the two drugs safely since the FDA approved the method in 2000.

But many women have used the drug vaginally, a delivery method the FDA has not evaluated.

Misoprostol is a synthetic version of a natural prostaglandin called E2. Prostaglandins are compounds that regulate the body’s immune response, and E2 can be a potent suppressor of that response, said Dr. David Aronoff, an infectious disease specialist who led the study.

His immunology lab began its study after the U.S. Centers for Disease Control reported in 2005 on four of the deaths, all of healthy women who died after medication abortions. Another had died as well.

"What struck me in those five cases is the women had previously been healthy, then died after taking fairly high doses of synthetic prostaglandin E2, which is misoprostol," Aranoff said.

"Vaginal application seems to be more effective, and women tolerate it better. It became quite popular," he added. "But in Europe they don’t use misoprostol vaginally, and no deaths had been reported there. We wondered if maybe high concentrations of this stable prostaglandin in the vaginal tract might lower a women’s ability to fight bacterial infections."

In animal and cell culture studies, the researchers found that when used vaginally, misoprostol can allow Clostridium sordellii, a normally non-threatening bacterium, to flourish and cause deadly infection. When absorbed through the stomach, however, the drug did not compromise immune defenses or cause illness.

Women rarely harbor the infection vaginally in the first place, Aranoff said, indicating an additional risk factor must exist in order for the infection to occur.

"It needs to be emphasized that the termination of pregnancy with these is drugs very safe," he said. "What our research does is maybe make a safe procedure even safer. These infections are very rare."

When taken orally, misoprostol gets absorbed into the bloodstream and distributed throughout the body. Vaginal use forces the drug to be absorbed initially in the soft tissue, leading to high concentration in one area before the subsequent absorption into the bloodstream.

Misoprostol is occasionally used as an immunosuppressant for organ transplant patients and most commonly as prevention against stomach ulcers by those taking high doses of aspirinlike compounds.

"Those patients show no immunosuppressant problems," Aranoff said. "That further substantiates how safe this drug is when taken by mouth."

In 2006 Planned Parenthood, the nation’s largest provider of abortions, stopped offering misoprostol vaginally as a precaution. The study supports that decision, Aranoff said.

It appears online ahead of print in the Journal of Immunology.