SYDNEY — Virtually every medicine is known to cause at least a few unintended side effects, but have you ever wondered how meds like aspirin or opioids may be affecting your immune system? Scientists from the University of Sydney investigated immune responses linked to acetaminophen (Tylenol), non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, and opioid analgesics with a specific focus on infectious diseases. The findings were mixed, remarkable, and hold major implications toward combating various infectious conditions – including COVID-19.
Some drugs appear to strengthen the body’s immune defenses against infections, while others can actually weaken the immune system. For example, morphine appears to suppress key immune cells and increase infection risk (especially after cancer surgery). Moreover, antipyretics — pain relief medications like acetaminophen (also known as paracetamol), ibuprofen, aspirin — also show a tendency to “reduce desirable immune responses when taken for vaccination.”
On the other hand, however, the study also finds Aspirin may offer therapeutic value as an affordable, accessible supplemental option for the treatment of tuberculosis. Moreover, study authors report the anti-inflammatory medicine indomethacin may impede viral COVID-19 replication. Further large-scale studies are required to confirm these initial findings.
“One of the problems is that widely used medicines –such as paracetamol, non-steroidal anti-inflammatory drugs like ibuprofen, and corticosteroids such as prednisone – have been around for decades and in the past we didn’t tend to consider their impacts on the immune system because it has been an under-recognized area,” concludes study co-author Professor Ric Day from UNSW and St Vincent’s Hospital, in a statement. “From community use to hospital and acute care, these classes of pain and fever medications are among the most popular drugs worldwide but we need to consider the significant impact these can have on our immune system and our response to infectious diseases, including COVID-19.”
‘Most important research I have been involved in’
Interestingly, this project all started as an investigation into solely acetaminophen during the pandemic. Many people hoarded the pain reliever during the early days and weeks of the COVID-19 pandemic.
“We decided to study painkillers and fever medications generally and were amazed by what we found,” says lead study author Dr. Christina Abdel-Shaheed. “In 14 years of studying pain, this is the most important research I have been involved in.”
All in all, the research team says this work is only the beginning. “Rigorous” clinical trials are the next logical step in terms of better understanding the complex relationships between pain medications and immune responses to infections.
“Our review shows some of the common pain and fever medications may work with the immune system to fight infection, whereas others work against it and increase the risk of contracting or responding badly to infectious diseases,” Dr Abdel-Shaheed explains. “Taking paracetamol or ibuprofen before or immediately after vaccination – for example for COVID-19 – to try to prevent mild fever or headache is not recommended, because this could reduce the body’s desirable immune response to the vaccine. For chickenpox, use of ibuprofen is not recommended as it might increase the risk of secondary bacterial skin infections.”
How pain relievers can be ‘repurposed’ when it comes to infectious diseases
According to Dr. Justin Beardsley, infectious disease specialist at Westmead Hospital and researcher with Sydney Institute for Infectious Diseases, this project’s findings regarding morphine specifically are of particular importance. “Morphine – one of the most commonly used opioid analgesics in post-surgical and critical care – suppresses key innate immunity cells, thereby increasing the risk of infection,” he explains. “This is particularly the case with cancer patients, who are already vulnerable to COVID-19.
“Efforts are needed to achieve adequate analgesia whilst avoiding immune-suppression in the immediate postoperative period caused by opioids such as morphine — both for people undergoing cancer surgery as well as for the immunocompromised generally,” Beardsley adds.
On a more positive note, Professor Andrew McLachlan, dean of pharmacy at the University of Sydney, says this new work opens the door for countless potential ways to “repurpose” pain meds to help with infectious disease treatments.
“With the urgent need for new treatments for COVID-19 and the declining efficacy of some antimicrobial agents due to resistance, now more than ever we need medicines which can maintain or enhance the efficacy of anti-infective drug treatments,” he adds. “The results of this review suggest that commonly used medicines for pain and fever should be further explored as inexpensive and effective adjunctive treatments which influence immune and inflammation pathways for people undergoing treatment for infection.”
The study is published in the British Journal of Clinical Pharmacology.