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Immune response to infection affected by pain and fever medications

By Rebecca Jenkins
Some common pain and fever medications might help the immune system fight infection, while others could increase the risk of contracting infectious diseases, Australian researchers warn.

In a large clinical review of research looking at immune responses to paracetamol, nonsteroidal anti­-inflammatory drugs (NSAIDs) and opioid analgesics, researchers from The University of Sydney’s Faculty of Medicine and Health uncovered a series of unintended immunological effects linked to the use of these medicines.

Antipyretic analgesics such as paracetamol and ibuprofen could reduce vaccine reactogenicity and vaccine immunogenicity, the review highlighted, with the researchers cautioning against prophylactic use of these drugs to prevent postvaccination headache, fever, or pain.

The review also found morphine, one of the most commonly used opioid analgesics in postsurgical and critical care, suppressed key cells of the innate immunity (including macrophages, neutrophils and mast cells) and increased the risk of infection.

‘Efforts are needed to achieve adequate analgesia whilst avoiding suppression of the innate immunity in the immediate postoperative period caused by certain opioids, particularly in cancer surgery,’ the researchers wrote in the British Journal of Clinical Pharmacology.

They also found evidence in animal models showing that NSAIDs had a beneficial role in Mycobacterium tuberculosis infection and histoplasmosis, but they cautioned this association needed to be tested in humans.

Lead author, Dr Christina Abdel Shaheed, an Academic Fellow at The University of Sydney with a special interest in pain research, said the review had challenged conventional thinking around commonly used medicine for pain and fever.

‘The implications are wide­-reaching as it affects people with cancer, the immunocompromised, the critically ill, people undergoing surgery and those with infection,’ she told Medicine Today.

Dr Abdel Shaheed noted the findings had implications for the COVID­-19 pandemic, with the review finding the NSAID indomethacin could reduce viral replication in SARS-CoV-2 in vitro and had shown some early promise in human clinical trials.

‘There is an urgent need to evaluate the use of this drug as host-directed therapy in SARS­-CoV­-2 [infection], particularly in the critically ill who may not be responding to the current best treatments,’ she said.

Coauthor Dr Justin Beardsley, an Infectious Disease Specialist at Sydney’s Westmead Hospital and a researcher at the Sydney Institute for Infectious Diseases, said clinicians did not usually consider immunological side effects when giving pain killers or antifever medications.

‘Our findings will help them make informed and evidence­ based decisions about when to use them,’ he told Medicine Today, saying particular care was needed when using these medicines in patients with infections.

‘Our findings also suggest possible clinical trial targets, where these medications could be repurposed to improve outcomes in infectious diseases.’
Br J Clin Pharmacol 2022; 1-18. https://doi.org/10.1111/bcp.15281.