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Title: Systematic analysis of the in vitro effects of exogenous opioids on innate and adaptive immune function
Author: Boland, Jason
ISNI:       0000 0004 2722 9120
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2011
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Background: Opioids are used to treat moderate to severe pain, including that associated with surgery, cancer and infection. Findings from a range of species and methodologies have demonstrated that whereas some opioids are immunoneutral (e.g. buprenorphine), others can be immunosuppressive (e.g. morphine) or immunostimulatory (e.g. tramadol). This study compared the effects of commonly used opioids on the potential to mount protective immunity against bacterial infections (neutrophil/monocyte phagocytosis and oxidative burst responses) and cancer (NK cell cytotoxicity/activation), as well as T cell activation and cytokine production. Methodology: Peripheral blood was obtained from healthy volunteers and the influence of clinically relevant concentrations of morphine, tramadol, fentanyl, buprenorphine, methadone, oxycodone, diamorphine and codeine on neutrophil and monocyte phagocytosis of E.coli and oxidative burst responses to fMLP, PMA and E.coli were determined by flow cytometry. Their effects on NK cell cytotoxicity in IL-2 stimulated, platelet-free peripheral blood mononuclear cells (PBMCs) and NK and T cell activation in IL-2 and anti-CD3/28 mAb stimulated PBMCs were also assessed. Cytokine production by anti-CD3/28 mAb and IL-2 stimulated PBMCs was determined using a cytometric bead array technique. Results: The only consistent, statistically significant effect was that methadone, oxycodone and diamorphine inhibited the production of IL-6 in IL-2 stimulated PBMCs, which could impair the acute phase response. There was however marked variability between individuals, both in their baseline and the effect of opioids, this was especially evident for morphine, tramadol, fentanyl and buprenorphine in the phagocytic and oxidative burst response to E.coli. Conclusion: These findings suggest that opioid choice could influence the susceptibility to bacterial or fungal infection, but have little effect on anti-cancer or anti-viral protection. Clinical studies aimed at assessing the in vivo effects of opioid administration on immune function in relevant patient groups are required in order to assess the clinical significance of opioid choice.
Supervisor: Pockley, Graham ; Ahmedzai, Sam Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available