A drug that inhibits the molecule known as prostaglandin E2 (PGE2) has been found to increase survival rates in mice infected with a lethal dose of the H1N1 flu virus, according to researchers at McGill University, Montreal.
The findings, which were published in the journal Immunity, pave the way for a therapy that is highly effective against the flu virus and potentially other viral infections, according to the authors.
“Drugs that specifically target PGE2 pathways have already been developed and tested in animals, so our results have excellent potential for clinical translation, not only for the treatment of influenza, but also other viral respiratory infections that interact with similar host immune pathways,” said Maziar Divangahi, senior author of the study.
Despite the worldwide use of vaccination and other antiviral interventions, the flu virus remains a persistent threat to human health. To investigate molecular pathways that could be targeted by novel interventions, Divangahi and his team became interested in ibuprofen, which is commonly used to manage flu-like symptoms.
By inhibiting a molecule called cyclooxygenase (COX), ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) lower the production of prostaglandins—immune molecules that contribute to pain and fever. But COX inhibition has produced conflicting effects on immune responses and survival rates in animals infected with the flu virus, highlighting the importance of clarifying the role of prostaglandins in antiviral immunity.
In the new study, Divangahi and his team found that mice genetically engineered to lack PGE2 showed enhanced immune responses, lower viral levels in the lungs, and better survival rates following infection with a lethal dose of the H1N1 flu virus compared with infected mice that were not genetically modified.
Similarly, mice treated with a compound that inhibits PGE2 showed enhanced antiviral immunity and survival rates following infection with a lethal dose of the flu virus compared with untreated mice.
“We believe that previous studies produced conflicting results because COX inhibition affects all prostaglandins, not just PGE2,” Divangahi said. “Our findings suggest that different prostaglandins have different roles in antiviral immunity and that specific inhibition of PGE2 will be much more effective than NSAIDs at protecting against influenza infection.”
