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Rheumatoid Arthritis Drug Might Fight Swine Flu
Date:5/29/2009

It helps regulate the immune system's response, study with mice shows

FRIDAY, May 29 (HealthDay News) -- Scientists are exploring the possibility that drugs that affect the immune system might one day serve as potent weapons to fight the flu, even the swine flu that's currently circulating around the globe.

The concept has worked with a group of lab mice that were treated with the rheumatoid arthritis drug abatacept (Orencia) after being given a lethal dose of influenza A virus, researchers report.

The mice were also loaded up with "memory" T-cells -- white blood cells that were programmed to react to this strain of flu.

Eighty percent of the treated mice lived, compared to only 50 percent of those left untreated, said Donna Farber, senior author of a paper published in the June 1 issue of The Journal of Immunology.

Basically, the drug enabled infection-fighting "memory" T cells to fight off the initial infection, but prevented them from overactivating the immune system, a process that can cause worse illness and even death.

The findings could have implications not only for the seasonal flu, which reappears with regularity each year, but for surprise outbreaks such as the swine flu.

"For the swine flu, there really are indications that you do get this sort of hyperimmune reaction," said Farber, who is a professor of surgery and microbiology and immunology at the University of Maryland School of Medicine in Baltimore. "Currently there is no treatment for people who are really ill from the flu, and there is already an indication that the immune system is too revved up [in these severe cases]. This could be a potential treatment for the flu."

The study was sponsored by Bristol-Myers Squibb, which makes Orencia, and the U.S. National Institutes of Health.

Orencia was approved for use in the United States in 2005 and introduced to the market in early 2006 to treat rheumatoid arthritis, an autoimmune disorder. It prevents activation of T lymphocytes, or white blood cells, whose function is to fight off infection.

"Memory" T-cells are a subset of T lymphocytes. They are "good" in that they can fight off an invading virus, but "bad" because they can also contribute to a hyperactive immune system that can lead to more illness and even death.

When a person becomes infected with a flu virus, the immune system dispatches these white blood cells to the lungs to get rid of the virus. But, if the cells don't know when to stop, they can cause tissue damage in the lungs, pneumonia and even death, Farber said.

"About half of your T-cells are memory T-cells. They persist and remember that you've seen a pathogen," she explained. "A response [to infection with the influenza virus] is likely to include some contribution of memory T-cells."

"With a lot of influenza, especially these pandemic strains, what really makes you sick and causes pneumonia is your immune response," Farber added.

The researchers injected mice with memory T-cells that had been programmed to react to an H1N1 strain of influenza A virus (the same "subtype" as the currently circulating swine flu) and then infected them with either a sub-lethal or lethal dose of the actual virus. In addition, at the start of infection, before the mice actually fell ill, half were given Orencia while the remaining half were left untreated.

In both sets of mice, those that had received Orencia cleared the virus quicker, got less sick and recovered faster than mice in the control group. The drug also tempered the immune response of the memory T-cells, the researchers found.

"It didn't dampen the immune response so much that it wasn't able to get rid of the virus but it tempered down the immune response," Farber said. "The mice didn't get as sick, they recovered a lot better and the lungs looked a lot healthier."

Orencia and similar drugs would have the added advantage of being effective against different strains of the flu virus because they're targeting the immune system, not the virus. The annual vaccine, on the other hand, is only effective against specific viral strains, the researchers said.

Robert Alaniz is an assistant professor of microbial and molecular pathogenesis at Texas A&M Health Science Center College of Medicine. He said, "Although the paper is a mouse study, the drug used is currently approved for human use and effective in humans. As far as I know, the use of abatacept has not been tested for its effects in humans infected with the flu, which is what makes this study novel and interesting.

"Although the results from this study are intriguing, much more work is warranted to ensure safety in humans infected with seasonal flu. However, the promise of the approach used in this study is that it maintains protective immunity against the virus while reducing disease pathology -- a very important point because overwhelming disease pathology is often a major contributing factor in flu-related deaths," he added.

More information

The U.S. Centers for Disease Control and Prevention has more on influenza.



SOURCES: Donna L. Farber, Ph.D., professor, surgery and microbiology and immunology, University of Maryland School of Medicine, Baltimore; Robert Alaniz, assistant professor, microbial and molecular pathogenesis, Texas A&M Health Science Center College of Medicine, College Station; June 1, 2009, The Journal of Immunology


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