In the article “Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica,” that was recently published in the journal Science, an international team of researchers identified the manner in which asbestos fibers cause scarring and damage to the lungs and to other body tissues. While the article does not specifically chart the path by which asbestos exposure leads to the development of cancers such as pleural mesothelioma, peritoneal mesothelioma or lung cancer, their findings are considered among the first to offer specific avenues in which to investigate this carcinogenic activity.

Overview of the Study

Although we’ve known for decades that asbestos causes cancer and lung damage, the precise biological processes by which the damage occurs have never been fully understood. Even as significant amounts of research were applied to the investigation of these mechanisms, the underlying biology has always remained mysterious, so the development of targeted therapeutics for those with asbestos exposure has remained merely a dream in the minds of scientists and patients. However, with the publication of this article, these researchers have provided a clear pathogenic path from asbestos exposure to lung damage and they have even proposed the use of a currently-approved drug as a means of treatment for those at risk.

The authors of the study applied their knowledge of the inflammatory activity they previously discovered was responsible for gout—an inflammation of the big toe and foot that is often quite painful—to the immune system’s response to asbestos exposure and determined that a similar complex of proteins, known as inflammasomes, was responsible for the tissue damage characteristic of exposure to asbestos fibers. When exposed to asbestos, the immune system stimulates the inflammasome Nalp3 to release interleukin-1b(IL-1B), a chemical responsible for inflammation. Because asbestos fibers do not easily break down, the researchers speculate that when the fibers become lodged in one’s system, they trigger the regular activation of Nalp3 and IL-1B, which leads to chronic inflammation and its attendant scarring and tissue damage. The researchers compared IL-1B levels and lung inflammation between normal mice exposed to asbestos and asbestos-exposed mice bred specifically to lack the Nalp3 inflammasome and they discovered the Nalp3-less mice demonstrated lower levels of IL-1B and less inflammation than did the normal mice, clearly showing a relationship between Nalp3, IL-1B and lung inflammation.

Along with these findings, they propose that Anakinra, a drug that blocks IL-1B expression and has already been approved for rheumatoid arthritis, could be given to those with known asbestos exposure. If their model is correct, then Anakinra should prevent tissue damage to those already suffering or at risk for developing asbestos-related disease. For the same reasons, Anakinra is already being investigated for a treatment of gout.

Conclusion

As is the case with every scientific study, further research needs to be completed to confirm the conclusions of the article. Assuming, however, that this confirmation does take place, these findings represent a very important step in our understanding of the biological mechanisms involved with asbestos disease. By identifying the immune system’s response to asbestos exposure, the researchers have discovered the starting point of the pathogenic process that often leads to the development of mesothelioma and lung cancer. An elaboration of these findings, then, will hopefully lead to a greater understanding of the underlying mechanisms of asbestos-related cancer genesis, as well as to the development of treatments that target these particular biological functions.

Labels: asbestos, mesothelioma