title: A preliminary evaluation of the effects of opioids on innate and adaptive human in vitro immune function.
abstract: BACKGROUND
  Studies have demonstrated that whereas some opioids have little effect on immunity (eg, buprenorphine), others can be immunosuppressive (eg, morphine) or immunostimulatory (eg, tramadol). However, a variety of approaches have been used, especially in vitro and animal models, and the findings are variable. We hypothesised that opioids have differential effects on immunity via direct actions on neutrophils, monocytes, natural killer (NK) and T cells, and this is the first study to systematically evaluate the influence of eight opioids on neutrophil and monocyte phagocytosis and oxidative burst responses, NK cell cytotoxicity and T cell responsiveness in vitro.
  
  
  METHODS
  Peripheral blood was obtained from healthy volunteers, and the effects of clinically relevant concentrations of morphine, tramadol, fentanyl, buprenorphine, methadone, oxycodone, diamorphine and codeine on phagocytosis and oxidative burst responses were determined using whole blood flow cytometry. The influence of opioids on the capacity of resting and IL-2 stimulated isolated peripheral blood mononuclear cells (PBMCs) to kill NK cell-sensitive K562 cells, and the responsiveness of PBMC subpopulations to IL-2 and polyclonal stimulation were also evaluated.
  
  
  RESULTS
  Methadone, oxycodone and diamorphine inhibited the production of IL-6 by IL-2 stimulated PBMCs. None of the opioids consistently influenced the other measured immune parameters, although there was a trend for morphine, tramadol, fentanyl and buprenorphine to inhibit phagocytosis and oxidative burst responses to Escherichia coli.
  
  
  CONCLUSIONS
  Preliminary studies using standardised in vitro methodologies have demonstrated that some therapeutic opioids suppress IL-6 production. Although this might potentially suppress bacterial defence mechanisms, it would have little direct effect on anticancer immunity. These findings should be confirmed in larger in vitro and clinical studies.
authors.affiliation: Department of Oncology, The Medical School, University of Sheffield, Sheffield, UK Hull York Medical School, University of Hull, Hull, UK.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Boland
authors.affiliation: Department of Oncology, The Medical School, University of Sheffield, Sheffield, UK.
authors.forename: Gemma A
authors.initials: GA
authors.lastname: Foulds
authors.affiliation: Department of Oncology, The Medical School, University of Sheffield, Sheffield, UK.
authors.forename: Sam H
authors.initials: SH
authors.lastname: Ahmedzai
authors.affiliation: Department of Oncology, The Medical School, University of Sheffield, Sheffield, UK John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, UK.
authors.forename: A Graham
authors.initials: AG
authors.lastname: Pockley
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology*; D002047:Buprenorphine / Q000494:pharmacology; D003061:Codeine / Q000276:immunology; D005283:Fentanyl / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008691:Methadone / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009020:Morphine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010098:Oxycodone / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D014147:Tramadol / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D007376:Interleukin-2; D015850:Interleukin-6; D014147:Tramadol; D002047:Buprenorphine; D009020:Morphine; D010098:Oxycodone; D008691:Methadone; D005283:Fentanyl; D003061:Codeine
keywords: Pharmacology; Supportive care; Symptoms and symptom management