AIDS Drug Thwarts Immune System

A potential AIDS drug called azodicarbonamide not only suppresses HIV but also the human immune system, scientists report in the August issue of Nature Medicine. Although some scientists think the discovery casts doubt on the drug's future in AIDS treatment, it points to its possible use in preventing the body from rejecting organ transplants.

In 1996, azodicarbonamide was discovered to inhibit HIV replication in cell cultures by interfering with the "zinc fingers"--elongated parts containing a zinc atom--of a crucial viral protein. It has been shown to work both in early and late stages of AIDS and is currently in clinical trials. Researchers at the Free University in Brussels, Belgium, wondered, however, whether the drug might also have an effect on the immune system--more specifically, on CD4 cells, the class of white blood cells infected by HIV.

The researchers used monoclonal antibodies to activate human CD4 cells in test tubes. They then measured the effect of azodicarbonamide on the cells' production of cytokines, proteins that signal other cells to mount their defenses. "We were surprised to see that this drug has a drastic effect," says team member Jamila Ismaili. In the majority of human samples tested, the drug reduced cytokine production by 80% to 90% within 72 hours.

The result led the researchers to think about an entirely different use for azodicarbonamide: as a drug that might stop the immune system from attacking transplanted organs. So in a second experiment, they gave a daily dose to mice that had received a skin transplant and monitored rejection. Without the drug, the skin transplants survived only 12 days; on average, azodicarbonamide doubled that. That suggests that azodicarbonamide can be added to the arsenal of immunosuppressive drugs, says Ismaili.

But the study raises questions about azodicarbonamide's use as an anti-HIV agent. "One might worry about additional immunosuppressive effects with AIDS," says Stephen Desiderio, a molecular biologist at the Johns Hopkins University School of Medicine. He points out that the drug could still be useful at the early stages of infection, when containing replication is more important than keeping the immune system in shape. "This is really a first look at the issue," says Desiderio.

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