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 immune defenses and make it easier for certain viruses to infect cells and spread. The findings, published in NAR Molecular Medicine, raise potential concerns for patients with active or latent viral infections, while also pointing to possible uses for the drugs in controlled laboratory research.
Anti-inflammatory drugs may help some viruses 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 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 that may be able to take advantage of these effects include Rift Valley fever virus, influenza A, adenovirus and SARS-CoV-2, the virus that causes COVID-19, Kainov said. These viruses can cause serious illness and may spread more readily when antiviral defenses are weakened.
How JAK inhibitors affect antiviral defenses
In the new study, 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 are effective at reducing inflammation, their benefits involve important trade-offs. By suppressing specific immune responses, JAK inhibitors may also interfere with mechanisms that normally protect healthy cells from viruses.
“Specifically, this drug suppresses important immune signaling pathways that help protect healthy cells from viral attack,” Lavro said.
These pathways help coordinate the body’s response when a virus attempts to infect healthy tissue.
Study identifies effects on immune-related genes
The researchers 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, an NTNU researcher and co-author of the paper.
When JAK inhibitors disrupt this immune-signaling system, they weaken an important layer of antiviral protection. Without a normal defense response, viruses may be more likely to establish an infection and spread between cells.
To investigate the effects, the team combined virology techniques with gene-expression analysis and organoid technology. The experiments included lung, eye and brain cells, as well as small organ models grown in the laboratory.
These methods allowed the researchers to examine how the drugs affect antiviral defenses in several 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 patients and future research
The findings highlight the importance of considering the potential risks of JAK inhibitors when patients may already have a viral infection or when viral infections are increasing in a population.
The researchers suggest that health care professionals should exercise caution when prescribing these drugs during periods when viral infections are on the rise.
At the same time, the immunosuppressive properties that may pose risks to patients could be useful in certain 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 research into the safest and most effective ways to use them.
“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