The pro-inflammatory cytokine TNF-? has been found to speed recovery of injured lungs and accelerate the resolution of established pulmonary fibrosis in a mouse model, according to researchers at National Jewish Health.
These findings, which were published in the American Journal of Respiratory Cell and Molecular Biology, suggest that a little inflammation may be crucial to the healing and repair processes in the lungs for conditions like pulmonary fibrosis.
“The role of inflammation in the development of scarring has been hotly debated in recent years,” said Elizabeth Redente, PhD, assistant professor of cell biology at National Jewish Health. “Our findings show for the first time that TNF-? actually promotes inflammation during the resolution of established scarring. A little inflammation may actually be a good thing in the right place and time.”
Idiopathic pulmonary fibrosis (IPF) affects about 128,100 people in the United States, with about 48,000 new cases diagnosed annually, according to statistics cited by the Coalition for Pulmonary Fibrosis. Approximately 40,000 people die each year as a result of IPF.
Redente and her colleagues gave mice TNF-? after their lungs had been injured and developed scar tissue. While these mice do normally heal from the lung injury, the researchers found that the TNF-? accelerated the recovery process. It reduced levels of collagen, the main component of scar tissue, and improved the flexibility of lung tissue well before the natural healing process would have begun. The researchers also found that knockout mice lacking the gene for TNF-? failed to heal as wild type mice eventually do.
The researchers believe that TNF-? acts by inducing white blood cells known as macrophages to change from ones that promote fibrosis to ones that promote inflammation instead. TNF-? may also promote the death of some of the pro-fibrotic macrophages.
“Physicians would welcome any therapy that could just slow down or stop the scarring process in the lungs,” said senior author David Riches, PhD, professor and head of the program in cell biology at National Jewish Health. “Our findings suggest that TNF-? not only slows the fibrotic process, but actually reverses established scarring in the lungs.”
The researchers are now investigating the role of TNF-? in various process that actually remove scar tissue including the removal of collagen-producing cells, the degradation and removal of collagen and restoration of healthy lung cells.