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Clearing the Air Over Asbestos

10 April 2008 (All day)
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Jürg Tschopp/University of Lausanne

Evildoer.
Scientists may have figured out how asbestos fibers (indicated by arrows and shown ensnared by an immune system cell) trigger lung scarring and cancer.

Researchers may have cracked the mystery of how asbestos causes life-threatening lung damage and cancer. A new study shows that the material triggers key immune system proteins that set off chronic inflammation. As a result, a commonly used arthritis drug might ward off the lung problems induced by exposure.

Over decades, asbestos fibers inhaled into the lungs can lead to cancer and scarring that interferes with breathing. Although these risks have been known for more than 100 years, researchers have been unable to uncover how the fibers, which are found in building materials and other products, trigger damage. Gout, a seemingly unrelated disease caused by the buildup of uric acid, may have provided a vital clue. Two years ago, a team led by biologist Jürg Tschopp of the University of Lausanne in Switzerland showed that uric acid causes gout by overactivating inflammasomes, immune proteins that spark inflammation to help wipe out germs. Might asbestos have a similar effect on the body?

Tschopp and colleagues exposed to asbestos human and mouse immune cells that lurk in the lungs. They found that the material stimulated an inflammasome called Nalp3 to release interleukin-1β (IL-1β), a chemical that incites inflammation. But the real proof came from mice that were bred to lack Nalp3. When these mice were exposed to asbestos for 9 days, they produced lower levels of IL-1β and less lung inflammation than did mice with Nalp3, confirming that the inflammasome is key to triggering at least some of the negative effects of the fiber, the researchers report online today in Science. Tschopp speculates that because asbestos fibers lodge in the body, prolonged exposure causes chronic inflammation that over time could result in lung scarring and cancer. The details still need to be worked out, but the researchers note that IL-1β has been linked to other cancers.

The findings suggest that the rheumatoid arthritis drug Anakinra, which blocks IL-1β and is being investigated as a gout treatment, could be used to prevent asbestos-triggered damage, says Tschopp. What's more, testing for elevated levels of IL-1β could allow doctors to identify people who are at risk of developing lung problems from asbestos exposure, adds Joseph Testa, a molecular geneticist at the Fox Chase Cancer Center in Philadelphia, Pennsylvania.

But David Kamp, a lung disease specialist at Northwestern University's Feinberg School of Medicine in Chicago, Illinois, cautions that it's too soon to say that we've discovered how the fibers cause cancer. The research did not show that this process provoked cancer in the mice, so scientists need to demonstrate the connection before looking ahead to treatments, he says.

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