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Pain medications ranging from over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) to hospital-prescribed morphine have a range of effects, not only on the conditions they’re intended to treat but on infectious disease paths and outcomes as well. A large clinical review of the immune system’s response to these medications sheds light on the sometimes surprising physiological impacts of commonly used drugs on infectious disease processes.
Scientists at the University of Sydney in Australia led a team that combed electronic databases for records and studies containing information on immune effects, infection, and various painkilling agents such as paracetamol (acetaminophen), NSAIDs, morphine, and oxycodone. They found that common drugs used to treat pain and fever can affect the immune system positively at times and negatively at times. The results were published in the British Journal of Clinical Pharmacology.
NSAIDs have consistently shown positive effects on Mycobacterium tuberculosis (Mtb) infection in animal studies. Aspirin’s anticoagulatory effects counter Mtb’s increased platelet activation, which can suppress immunity. Other NSAIDs such as ibuprofen and indomethacin have shown beneficial impacts on immune responses to Mtb and other infections in animals and in in vitro human studies. Yet in the case of Streptococcus pyogenes infection in mouse models, these same NSAIDs were shown to increase the severity of infection. And studies of the effects of NSAIDs on patients infected with COVID-19 also yield conflicting results.
According to the study’s authors, NSAIDs seem to improve cell-mediated immunity but inhibit humoral, or antibody-mediated, immunity. “This was an interesting finding and was determined predominantly from laboratory data,” Dr. Christina Abdel-Shaheed, early career development fellow at the University of Sydney School of Public Health, and the paper’s lead author, told Contagion. “The implications of these findings need to be further explored in the context of specific infections and in people who may be using these medicines following vaccination.”
It seems clear, however, that NSAIDs may do more harm than good if taken before vaccination in order to head off injection-site pain and fever; in vitro studies reveal that aspirin, ibuprofen, and naproxen can blunt these aggravating but important side effects that show a vaccine is working as intended. “Antipyretic analgesics (NSAIDs or paracetamol) are not recommended prior to vaccination as they can reduce the desirable immune response to the vaccine (ie, reduce antibody levels),” said Abdel-Shaheed. “They can be used after vaccination to treat pain, headache, or fever, and should ideally be reserved for severe symptoms.”
Of particular concern is cancer patients and other high-risk individuals who may receive morphine post surgery or in a critical-care setting. Studies found that morphine can depress immune activity and raise the risk of serious infection in these patients. While the topic needs urgent attention, according to Abdel-Shaheed, there is not yet enough data to influence clinical guidance. While alternative opioids such as tramadol and tapentadol seem to be less harmful, she said, the impact of those drugs has not been sufficiently studied.
Future research will focus on the use of NSAIDs, particularly aspirin, in treating tuberculosis; the use of indomethacin as a potential COVID-19 therapy; and painkillers other than morphine to treat high-risk patients in surgical and critical-care units. Abdel-Shaheed said it’s also important to raise awareness of morphine’s association with increased risk of infection and teach healthcare staff to diligently monitor vulnerable patients who receive the drug.