Effect of opioids on the phagocytosis of neutrophils and monocytes: a systematic in vitro analysis

Abstract

Background Bacterial infection is a common complication in patients with advanced disease, including cancer. Ingestion (phagocytosis) and subsequent killing of bacteria by neutrophils and monocytes are critical in the control of infection. Using a range of different methodologies, previous invitro and in vivo studies have generally reported that some commonly prescribed opioids are immunosuppressive (ie, morphine), whereas others have been shown to be immunoneutral (ie, fentanyl), and even immunostimulatory (ie, tramadol). However, direct, comparative, systematic studies aimed at analysing their relative impact remain lacking. Aims To systematically assess the in vitro effects of clinically-relevant concentrations of commonly used opioids on the phagocytosis of E coli by peripheral blood neutrophils and monocytes. Methods Peripheral blood was collected from healthy volunteers and incubated with clinically-relevant concentrations of morphine, fentanyl, tramadol, buprenorphine, oxycodone, diamorphine, methadone or codeine for 60 min. Samples were then incubated with FITC-conjugated E.coli for 10 min at 37°C, at which time the proportion of neutrophils and monocytes that had phagocytosed E.coli, and the intensity of the phagocytic response was determined using whole blood flow cytometry (PHAGOTEST, Orpegen Pharma GmbH, Germany). Control samples were incubated at 4°C. Results Although morphine, fentanyl, tramadol and buprenorphine inhibited the phagocytic responses of neutrophils and monocytes by up to 75% in some individuals, due to inter-individual variability this did not reach statistical significance. Codeine, oxycodone, diamorphine and methadone had no detectable effect on neutrophil or monocyte phagocytosis. Conclusion Although the true impact of opioid treatment on the susceptibility of patients to bacterial infection in vivo has yet to be defined, these systematically observed in vitro findings indicate that opioid choice might impact on the clinical status of some patients who are at an increased risk of bacterial infection. Future work needs to elucidate the population prevalence to the susceptibility from these potentially immunosuppressive opioids.

Monocytes in the Characterization of Pain in Palliative Patients with Severe Dementia—A Pilot Study

“…Freshly isolated peripheral blood monocytes express a relatively low level of CD163, but this expression increases with the differentiation of such cells into macrophages [ 26 ], a role assigned mainly to intermediate monocytes [ 11 , 36 ]. Our results confirm that opioids may substantially affect monocytes’ inactivation, as shown by others [ 38 , 39 ], confirming their anti-inflammatory effect. On the other hand, in patients receiving paracetamol, only an increase in the ratio of CD163/CD206 was detected in non-classic monocytes.…”

Association between IL‐10 systemic low level and highest pain score in patients during symptomatic SARS‐CoV‐2 infection

“…31 Codeine does not produce a detectable influence on immune responses. 32 As mentioned above, the dose of codeine used (10 mg) was lower than its analgesic dose (ranging from 15 to 60 mg), thus, it is also reasonable that codeine dose was not as analgesic as it could be. This would normally occur in a disease of lesser intensity, but as there is an intense inflammatory response in Covid-19, the standard dose may not have been sufficient to reduce the production of the biological markers evaluated, and consequently, interfere with the pain perception.…”

“…In general, most of the studies demonstrated morphine suppresses the production of cytokines by macrophages and T cells 31 . Codeine does not produce a detectable influence on immune responses 32 . As mentioned above, the dose of codeine used (10 mg) was lower than its analgesic dose (ranging from 15 to 60 mg), thus, it is also reasonable that codeine dose was not as analgesic as it could be.…”

A double-edged sword of using opioids and COVID-19: a toxicological view

“…In contrast, codeine, oxycodone, diamorphine, and methadone did not produce a measurable effect on the immune system [ 19 ]. Another related study indicated that morphine leads to the induction of apoptosis in the immune cells, atrophy of the thymus and spleen, and suppression of proliferation of B and T lymphocytes [ 20 ].…”