Iwona Filipczak-Bryniarska1, Katarzyna Nazimek2, Bernadeta Nowak2, Michael Kozlowski3, Magdalena Wąsik2, Krzysztof Bryniarski4. 1. Department of Pain Treatment and Palliative Care, Jagiellonian University Medical College, 10 Sniadeckich St, PL 31-531 Krakow, Poland. 2. Department of Immunology, Jagiellonian University Medical College, 18 Czysta St, PL 31-121 Krakow, Poland. 3. Department of Pain Treatment and Palliative Care, Jagiellonian University Medical College, 10 Sniadeckich St, PL 31-531 Krakow, Poland; Department of Immunology, Jagiellonian University Medical College, 18 Czysta St, PL 31-121 Krakow, Poland. 4. Department of Immunology, Jagiellonian University Medical College, 18 Czysta St, PL 31-121 Krakow, Poland. Electronic address: krzysztof.bryniarski@uj.edu.pl.
Abstract
BACKGROUND: Opioid receptors are commonly expressed on various immune cells, macrophages especially. Thus, these cells are prone to stimulation with opioids, which seems to be responsible for opioid-induced immunomodulatory effects. While morphine, fentanyl and methadone influence on mouse immune response was recently studied, little is known about the potential immunomodulatory impact of buprenorphine and oxycodone. AIM: The current research aimed to investigate the influence of buprenorphine and oxycodone on immune responses in mice under homeostatic conditions. METHODS AND RESULTS: Repeated administration of morphine led to intensification of CHS response in actively sensitized mice, while buprenorphine or oxycodone administration exerted the opposite effect. Further, hapten-conjugated macrophages from mice treated with morphine, when transferred into naive recipients, induced more potent CHS response. The enhanced generation of reactive oxygen intermediates and nitric oxide by macrophages from mice treated with buprenorphine, oxycodone or morphine was also shown, along with increased release of IL-6, TNFα and TGFβ. Treatment with opioids altered expression of antigen phagocytosis and presentation markers. Finally, the inhibitory effect of morphine treatment on induction of humoral immunity by macrophages was demonstrated, while oxycodone failed to influence humoral immune response and buprenorphine actually enhanced B-cell activation. CONCLUSIONS: Current observations confirm that macrophages greatly contribute to immunomodulatory effects of opioids. Studies on immunomodulation by opioids have great importance related to the evaluation of its beneficial and adverse effects on patient condition. Our research showed that oxycodone exerts the weakest immunomodulatory properties, allowing us to assume this drug as safer than morphine during prolonged therapy.
BACKGROUND: Opioid receptors are commonly expressed on various immune cells, macrophages especially. Thus, these cells are prone to stimulation with opioids, which seems to be responsible for opioid-induced immunomodulatory effects. While morphine, fentanyl and methadone influence on mouse immune response was recently studied, little is known about the potential immunomodulatory impact of buprenorphine and oxycodone. AIM: The current research aimed to investigate the influence of buprenorphine and oxycodone on immune responses in mice under homeostatic conditions. METHODS AND RESULTS: Repeated administration of morphine led to intensification of CHS response in actively sensitized mice, while buprenorphine or oxycodone administration exerted the opposite effect. Further, hapten-conjugated macrophages from mice treated with morphine, when transferred into naive recipients, induced more potent CHS response. The enhanced generation of reactive oxygen intermediates and nitric oxide by macrophages from mice treated with buprenorphine, oxycodone or morphine was also shown, along with increased release of IL-6, TNFα and TGFβ. Treatment with opioids altered expression of antigen phagocytosis and presentation markers. Finally, the inhibitory effect of morphine treatment on induction of humoral immunity by macrophages was demonstrated, while oxycodone failed to influence humoral immune response and buprenorphine actually enhanced B-cell activation. CONCLUSIONS: Current observations confirm that macrophages greatly contribute to immunomodulatory effects of opioids. Studies on immunomodulation by opioids have great importance related to the evaluation of its beneficial and adverse effects on patient condition. Our research showed that oxycodone exerts the weakest immunomodulatory properties, allowing us to assume this drug as safer than morphine during prolonged therapy.
Authors: Iwona Filipczak-Bryniarska; Katarzyna Nazimek; Bernadeta Nowak; Michael Kozlowski; Magdalena Wąsik; Krzysztof Bryniarski Journal: Data Brief Date: 2017-12-13
Authors: Kyle G Hawkins; Caleb Casolaro; Jacquelyn A Brown; David A Edwards; John P Wikswo Journal: Clin Pharmacol Ther Date: 2020-05-29 Impact factor: 6.875