Scientists at the Norwegian University of Science and Technology (NTNU) have discovered that a widely used class of anti-inflammatory medications may make it easier for certain viruses to infect cells and spread throughout the body.
They suggest that JAK inhibitors, prescribed for rheumatoid arthritis and other inflammatory diseases, can weaken a crucial immune defence against influenza, Covid-19, and other infections. By suppressing genes that normally fight viruses, they may, in fact, leave patients more vulnerable to infection.
While side effects are common with many treatments, the team identified a particularly concerning, and surprising, possibility involving these drugs, said Denis Kainov, a professor at the NTNU’s Department of Clinical and Molecular Medicine.
The medications are Janus kinase inhibitors, or JAKs, widely prescribed to control inflammation.
“Among the viruses that more easily affect the body with the help of these drugs are Rift Valley fever virus, influenza A, adenovirus and SARS-CoV-2,” said Kainov.
Why arthritis drugs can weaken antiviral defences
“JAK inhibitors are often prescribed for autoimmune diseases and inflammatory conditions like rheumatoid arthritis,” said Erlend Ravlo, a PhD research fellow at NTNU and first author of the study, published in NAR Molecular Medicine.
Although these medications can be highly effective at reducing inflammation, their benefits come with an important trade-off. By suppressing certain immune responses, they can also interfere with the mechanisms that normally protect the body from viral infections.
“In particular, the drugs suppress an important immune signalling pathway that helps protect healthy cells from viral attacks,” Ravlo said. This pathway plays a central role in co-ordinating the body’s response when viruses attempt to infect healthy tissue.
The team found that JAK inhibitors, including the medication baricitinib, can reduce the activity of genes involved in fighting these infections.
When JAK inhibitors interfere with this immune signalling system, they weaken an important layer of antiviral protection.
To investigate these effects, the scientists combined advanced virology methods with gene expression analysis and organoid technology. Their experiments included cells from the lungs, eyes and brain, along with miniature organ models grown in the laboratory.
What the findings mean for patients
The results highlight the importance of carefully considering the risks associated with JAK inhibitors, particularly when patients may already have a viral infection or when outbreaks are occurring.
The researchers suggest healthcare professionals should exercise caution when prescribing the drugs during periods of increased viral transmission.
However, the same immune-suppressing properties that create potential risks for patients could also offer advantages in certain research settings. Under controlled laboratory conditions, these effects may help scientists develop vaccines or evaluate potential antiviral medications.
The researchers recommend further studies to better understand how the drugs can be used optimally, especially during virus outbreaks or pandemics.
Study details:
JAK inhibitors remove innate immune barriers facilitating viral propagation
Erlend Ravlo, Aleksandr Ianevski, Marius Nårstad Skipperstøen et al.
Published in NAR Molecular Medicine Volume 2 Issue 2
Abstract
Janus kinase (JAK) inhibitors are small-molecule therapeutics that reduce inflammation in autoimmune and inflammatory diseases by modulating the JAK–STAT pathway. While effective in alleviating immune-mediated conditions, JAK inhibitors can impair antiviral defences by suppressing interferon (IFN) responses, potentially increasing susceptibility to viral infections. This study investigates the pro-viral mechanism of JAK inhibitors, focusing on baricitinib, across various cell lines, organoids, and viral strains, including a recombinant Rift Valley fever virus, influenza A virus, SARS-CoV-2, and wild-type adenovirus. Our findings demonstrate that baricitinib suppresses transcription of IFN-stimulated genes in non-infected cells, which is triggered by type I IFNs produced by infected cells, facilitating viral propagation. The pro-viral effect was influenced by viral load, inhibitor concentration, and structural characteristics of the compound. These results underscore the dual effects of JAK inhibitors: reducing inflammation while potentially exacerbating viral infections. Additionally, the findings highlight opportunities to leverage JAK inhibitors for viral research, vaccine production, and drug screening.
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