LONDON (Reuter) - German scientists said Wednesday they had found a substance, naturally produced by the body's immune system, which slows down reproduction of the HIV virus that causes AIDS.
AIDS experts cautioned against greeting the finding of this suppressor as a breakthrough. But they said it may be a very important discovery that could lead to treatments for and, possibly, a vaccine against the deadly virus.
A report in the scientific journal Nature said interleukin-16, which helps the body's immune cells manufacture antibodies, acted as a natural defense against HIV.
Reinhard Kurth and colleagues at the Paul-Ehrlich-Institut in Langen, Germany, said they had found that interleukin-16, which is secreted by ``suppressor'' T-cells known as CD8 cells, slowed down the reproduction of HIV viruses.
This happened at the highest rate when HIV sufferers still showed no symptoms of AIDS, they said.
``This antiviral activity is positively correlated with the health of HIV-infected patients and is high during the asymptomatic stages of infection,'' they wrote.
HIV is especially complicated to fight off because the virus attacks the T-cells.
The scientists added that African green monkeys, which often carry their own version of the virus known as SIV, never get the ape and monkey version of AIDS (Simian Immune Deficiency Syndrome). Their interleukin-16 is similar to human interleukin-16.
``The potential implications of this study are substantial,'' said Anthony Fauci of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
Fauci said scientists have known for some time that something in the ``suppressor'' T-cells was inhibiting the replication of the virus, but no one knew what it was.
``We need to do some basic studies to find the basic mechanism, and then do animal studies,'' Fauci said in a telephone interview.
Fauci said interleukin might eventually be used as an immune system booster -- similar to gamma globulin which is given to people to boost their immune systems against certain forms of hepatitis. Not quite a vaccine, it works in a similar way.
He said the African green monkeys could serve as a good model ``if this works the same in the monkeys as it does in humans. We have got to make sure we are careful and not declare a breakthrough.''
There are several types of T-cells in the body's immune system. Some are ``killer'' cells and attack invaders such as viruses or cells that have been damaged.
Others are known as ``helper'' or ``suppressor'' cells.
Interleukins, secreted by the ``suppressor'' cells, stimulate the production of antibodies. These attach themselves to foreign invaders, allowing the killer cells to recognize and destroy them.
Scientists hope that if the T-cells can be helped to protect themselves, the body can more easily fight off AIDS.
Two groups of scientists are reporting that they have identified long-sought chemicals produced by the immune system that in laboratory experiments have stopped the AIDS virus in its tracks.
AIDS researchers said that discoveries, reported in papers released yesterday afternoon by two major scientific journals, could have profound implications for the prevention and treatment of infections with the human immunodeficiency virus, which causes AIDS.
The notion that there was something produced by the body that in some cases stopped H.I.V. from reproducing was first suggested a decade ago by Dr. Jay Levy of the University of California in San Francisco, but the substance itself had proved elusive and many scientists had doubted that it existed.
The new reports described not one chemical but several, all of them released by white blood cells, and none of them understood. Both reports assert that in laboratory tissue cultures of human cells, one or more of these natural chemicals stop H.I.V. from replicating.
The research done so far is basic, and any application to treating people with AIDS would be far down the road.
"From a conceptual stand point, it's very important," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. But, Dr. Fauci cautioned, people should be wary of assuming that these chemicals will be useful as a treatment. More than a decade of experience with AIDS has taught him, he said, that many things that look great in the test tube, "never make it to the major league."
Dr. Bruce Walker, director of AIDS research at the Massachusetts General Hospital in Boston, said, "It's very exciting." But, Dr. Walker also urged caution, saying that the chemicals "may have other effects on the body, including potentially toxic effects, if given in large amounts."
Nonetheless, AIDS researchers say, the current reports clearly open new pathways for research, apart from treatment. The findings may offer clues to why the virus never takes hold in some people who are repeatedly exposed to it through risky behavior, and why, even among infected people, some live into a second decade without becoming ill while others fall ill within a few years of an H.I.V. infection. In addition, the action of these immune system chemicals might help explain the central mystery of AIDS vaccine research: what reaction by the body must a vaccine elicit to protect against H.I.V. infections?
Even as the discoveries are creating a buzz among researchers, they reveal the intense rivalries in this field.
One of the papers was rushed into print as a letter to the editor rather than a full article in the journal Nature when its author, Dr. Reinhard Kurth, president of the Paul Erlich Institute in Langen, Germany, realized that he had competition. He learned that Dr. Robert C. Gallo, formerly of the National Cancer Institute and now director of the Institute for Human Virology at the University of Maryland, had a similar result.
Dr. Gallo's paper, to be published in the Dec. 15 issue of the journal Science, was released yesterday evening to share the spotlight with Dr. Kurth's paper.
Moreover, the two groups have found different substances. Dr. Gallo and his colleagues, including Dr. Paolo Lusso, who is now at the San Raffaele Scientific Institute in Milan, report the effects of three chemicals known as chemokines, which are released by one type of white blood cell when a foreign substance in the body produces an inflammation. The chemokines had never been linked to antiviral action. But the new study showed that in concert they stop H.I.V. from growing.
Dr. Kurth and his colleagues report, from studies of African green monkeys, on a product of white blood cells in these monkeys, a hormone known as interleukin 16, also involved in the immune system's inflammatory response. Interleukin 16, according to this study, also stops the H.I.V. Human cells produce a nearly identical hormone.
Reactions to the papers are mixed. Dr. Gallo's paper, said Dr. John Moore, an immunologist at the Aaron Diamond AIDS Research Center in New York, "looks to be a super piece of work." Dr. Kurth's paper, he said, "looks rushed," adding that the data presented in the letter in Nature did not convince him.
Dr. Gallo dismissed Dr. Kurth's work, saying, "Kurth's working with monkeys; we're working with humans. His is a letter; ours is a paper. What can I say?"
Dr. Fauci, who wrote an editorial accompanying Dr. Kurth's work, said it was possible that both groups were correct.
Dr. Kurth, aware of the criticisms of his letter, said in a telephone interview: "We are sitting on a wealth of data that will soon be submitted." And Dr. Levy, who first suggested that such substances existed, said in a telephone interview from Brazil, where he was vacationing, that he was not convinced that either group had found the elusive "soluble factor" he had been seeking.
He said he began his research when he found that he could not always isolate H.I.V. from white blood cells of people infected with the virus. "We asked, why?" he said.
Soon, Dr. Levy proposed what was to become a disputed hypothesis: that a type of white blood cell called CD8 could release a substance that held H.I.V. in abeyance. As long as CD8 cells are making the substance, he hypothesized, the virus is unable to grow. When the substance is removed, the infection roars back.
"It took a long time for people to believe it," Dr. Levy said. Facing widespread skepticism, he nonetheless persisted, spending the past decade trying to isolate the substance. But he has yet to discover what it is.
Dr. Gallo said he became interested in this line of inquiry because of his frustration with AIDS vaccine research. Investigators testing vaccines in monkeys had found that some animals were protected against infection but others were not. But they did not know what made the difference between immunity and susceptibility to infection in vaccinated animals. Antibodies made no difference. Neither did levels of virus-killing white blood cells.
"The No. 1 reason that we don't have a vaccine today is that we don't know what to induce in humans," Dr. Gallo said. "That's what drove me to look" for a product of white blood cells, he added.
So, he said, he decided to grow CD8 cells in large quantities and isolate the substance or substances responsible for stopping H.I.V. And, he said, once he got the CD8 cells growing and producing the substances, "In a few steps, it was over."
Dr. Gallo said he discovered that three chemokines, known as Rantes, MIP-1alpha, and MIP-1beta together inhibited H.I.V. If he added even a tiny amount of the three chemicals, he said, H.I.V. could not grow. But all three were necessary. If even one of the three were blocked from biochemical activity with antibodies that attached to them, the virus could replicate.
Dr. Kurth focused on African green monkeys because they do not become ill from the monkey form of H.I.V., although Asian monkeys do. He suspected that whatever the CD8 cell was producing might be the reason. In his letter, he reports that CD8 cells of the African monkey secrete the hormone interleukin 16. And, he found, the hormone, in relatively high concentrations, can suppress the growth of both the monkey virus and H.I.V. in the laboratory.
Now, AIDS researchers said, laboratories throughout the world will be rushing to replicate the new discoveries and to investigate their implications.
Dr. Dani Bolognesi, an AIDS vaccine researcher at Duke University, noted that Dr. Gallo's paper, in particular, "will activate a lot of research."
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