Recently, international investigative teams discovered a novel way to potentially stop lung scarring.
Science Translational Medicine
Part of the body’s immune response to tissue injury, interleukin-11 (IL-11) is a signaling protein known to be involved in fibrosis (scarring) of the kidneys and heart.
While it has been unclear whether IL-11 is pro- or antifibrotic, a new study showed that people with IPF have higher IL-11 activity in fibroblasts of the lungs, causing these cells to become myofibroblasts, destroy lung tissue, and form scar.* Researchers from Singapore, Europe, and the US demonstrated that IL-11 is secreted in greater amounts by lung fibroblasts in people with IPF, and that disease severity is linked to IL-11 activity.
- Examining lung tissue of IPF patients (in vitro), they showed that IL-11 stimulates lung fibroblasts to become myofibroblasts that secrete collagen—an important component inducing fibrosis.
- Examining mice (in vivo), they saw that injecting IL-11 led to lung myofibroblasts and fibrosis.
- The researchers saw that removing IL-11 receptors on lung fibroblasts protected mice with PF from profibrotic signaling and scar formation.
- Teams then used a therapeutic antibody drug to bind IL-11, neutralizing it, and block the lung fibroblast-to-myofibroblast activation process.
- Antibody treatment reduced lung inflammation and “reversed” fibrosis as it blocked profibrotic signaling in a mouse model of pulmonary fibrosis. Extension to human fibrotic diseases needs to be investigated.
British Lung Foundation chair Toby Maher explained the study’s importance in a news release, stating,
“We desperately need new therapies to genuinely transform outcomes for people with IPF. This exciting research highlights the importance of IL-11 in driving the development of fibrosis and gives hope for a new treatment approach to halt and maybe even reverse the devastating lung scarring of IPF.”
Lead author Stuart Cook of the MRC London Institute of Medical Sciences said the group aims to test the antibodies in human safety trials by the close of next year and begin IPF patient clinical trials in 2021.
The research article can be found at:
*Ng, B.; Dong, J.; D’Agostino; et al. (2019). Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. Science Translational Medicine, 11(511).