Asbestos is the top cause worldwide of malignant pleural mesothelioma, a rare but difficult-to-treat cancer that often kills patients within a year of diagnosis. When they are inhaled, asbestos fibers lodge in the lugs triggering irritation and inflammation that eventually causes cells to become malignant. But the exact mechanism that moves cells from irritation to mesothelioma is still poorly understood.
Now, researchers in Brazil have uncovered another piece of the puzzle that may help explain how mesothelioma develops. According to a new published report, they have isolated two small signaling proteins called cytokines that appear to be responsible for deadly asbestos-induced inflammation, the death and mutation of healthy cells and, eventually, mesothelioma.
Doctors at the University of Sao Paulo Medical School exposed cells from the pleural mesothelium of mice to two types of asbestos fibers for 4, 24, or 48 hours. Afterward, they assessed the cells’ viability and the production of cytokines and found that, not only did the asbestos-exposed cells over produce inflammatory cytokines, but they also underwent apoptosis (programmed death) and necrosis (death from injury) at higher rates.
“Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1β, IL-6 and MIP-2 [cytokines],” reports the study’s lead author Milena M. Acencio.
To confirm their theory that these cytokines were responsible for the type of inflammatory response that can lead to mesothelioma, they neutralized the cytokines with antibodies to effectively “turn off” their signaling. They found that neutralization of these proteins inhibited the death of the healthy mesothelial cells.The authors conclude that cytokines “contribute to asbestos-induced injury”, paving the way for a better understanding of mesothelioma.
The new research was published in the journal Lung.
Acencio, MM, et al “Inflammatory cytokines contribute to asbestos-induced injury of mesothelial cells”, June 10, 2015, Lung, Epub ahead of print