A protein that is currently being tested as a potential treatment for COVID-19 may be helpful in fighting the virus, but new research shows that it can also suppress lung damage repair.
In response to a viral infection in the lungs, the immune system activates a protein called interferon lambda to launch a defensive attack. Once activated, interferon lambda signals to surrounding lung tissue cells to switch on antiviral defenses.
Researchers at the Francis Crick Institute have found that while interferon lambda is initially effective in helping the body defend itself from the virus, it can interfere with the repair of lung damage if it remains active for an extended time period.
The researchers used a mouse model to investigate the effects of activating interferon lambda in mice with influenza. The study revealed that elevated levels of the protein caused epithelial cells to multiply less frequently. The outcome was the same for mice that had produced interferon lambda naturally in response to the virus and for mice who were ingested with the protein.
A lab experiment showed that human epithelial cells treated with interferon lambda were also adversely affected.
Epithelial cells make up the lining of the airspaces in the lungs and have many important functions, such as multiplying to replace damaged cells. The suppression of epithelial cell division by interferon lambda could prolong lung damage and increase the risk of bacterial infections.
“This is a really potent protein with many different functions,” said study co-author Andreas Wack. “At the beginning of a viral infection, it is protective, triggering functions that help to fight the virus. However, if it remains in the tissue for too long, it could become harmful.”
“This means, for any antiviral treatment that uses this protein, there is a really careful balance that must be made. Clinicians should consider the timing of the treatment, the earlier this better, and the duration of treatment.”
Even though the research was focused on mice infected with influenza, the protein would cause similar effects for other viruses that also cause lung damage, including COVID-19.
The paper has been published in the journal Science alongside research from Harvard Medical School, which found that patients with severe COVID-19 infections showed strong expression of interferon lambda in their lungs.
“Understanding how our bodies respond to infection has never been more important. Differences in our immune responses have huge implications for whether a treatment will work and what the side effects might be,” said Jack Major, lead author of the Crick study.
“Our results suggest that before pursuing treatment with interferon lambda, doctors should consider at what stage of the disease patients are, as treatment late in infection may increase the risk of prolonged damage.”
The study is published in the journal Science.