Researchers at the Norwegian University of Science and Technology (NTNU) have found that Janus kinase (JAK) inhibitors, a widely used class of anti-inflammatory drugs, may weaken antiviral defenses and make it easier for certain viruses to infect cells and spread through the body. The findings raise concerns about their use in patients with active or latent viral infections, while also pointing to possible applications in vaccine and antiviral-drug research.
Anti-inflammatory drugs may aid viral spread
JAK inhibitors are commonly prescribed to control inflammation associated with autoimmune diseases and rheumatoid arthritis. However, because they suppress parts of the immune system, they may also leave the body more vulnerable to some viral infections.
“We found that certain anti-inflammatory drugs have surprising and potentially serious side effects. Anti-inflammatory drugs may help the virus spread more easily in the body,” said Professor Denis Kainov of NTNU’s Department of Clinical and Molecular Medicine.
The viruses identified as potentially easier to spread with the help of these drugs include Rift Valley fever virus, influenza A, adenovirus and SARS-CoV-2, the virus that causes COVID-19, Kainov said.
How JAK inhibitors affect antiviral defenses
In a study published in NAR Molecular Medicine, Kainov and his colleagues examined how JAK inhibitors affect the body’s ability to respond to viral infections.
“JAK inhibitors are often prescribed for inflammatory conditions such as autoimmune diseases and rheumatoid arthritis,” said Erlend Lavro, a postdoctoral fellow at NTNU and the paper’s lead author.
Although the drugs can effectively reduce inflammation, they also suppress immune responses that help protect healthy cells from viral attack.
“Specifically, this drug suppresses important immune signaling pathways that help protect healthy cells from viral attack,” Lavro said.
These signaling pathways help coordinate the body’s response when a virus attempts to infect healthy tissue. Disrupting them can weaken an important layer of antiviral protection, potentially allowing viruses to establish infections and spread between cells.
Study examined several types of human tissue
The research team found that JAK inhibitors, including baricitinib, can reduce the activity of genes involved in fighting viral infections.
“These genes play an important role in the body’s response to viral infections,” said Alexander Ianevsky, a researcher at NTNU and a co-author of the paper.
To study the effects, the scientists combined virology techniques with gene-expression analysis and organoid technology. Their experiments involved lung, eye and brain cells, along with small organ models grown in the laboratory.
Using these methods, the researchers examined how JAK inhibitors affect antiviral defenses in different types of human tissue.
“While JAK inhibitors are effective in treating inflammation, this shows that they may pose hidden risks for patients with latent or active viral infections,” Lavro said.
Implications for treatment and research
The findings underscore the need to consider the potential risks of JAK inhibitors when patients may already have a viral infection or when viral outbreaks are occurring. The researchers suggest that health care professionals should exercise caution when prescribing the drugs during periods when viral infections are increasing.
At the same time, the immunosuppressive properties that may pose risks to patients could be useful in some research settings. Under controlled laboratory conditions, these effects could help scientists develop vaccines or evaluate potential antiviral drugs.
The researchers hope the findings will increase awareness of how JAK inhibitors affect the immune system and encourage further work on using the drugs as safely and effectively as possible.
“We recommend further research to better understand how the drug can be optimally used, especially during viral outbreaks and pandemics,” Ianevsky said.
Professor Magnar Bjørås of NTNU’s Department of Clinical Molecular Medicine provided scientific expertise and secured most of the research funding. Additional support came from the Central Norway Regional Health Authority, the South-East Norway Regional Health Authority, the Norwegian Research Council and the Swedish Research Council.
Source: www.sciencedaily.com
