buprenorphine and Dermatitis--Contact

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.. The current research aimed to investigate the influence of buprenorphine and oxycodone on immune responses in mice under homeostatic conditions.. 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.. 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.

Topics: Animals; Buprenorphine; Cells, Cultured; Cytokines; Dermatitis, Contact; Homeostasis; Humans; Immunity, Cellular; Immunity, Humoral; Immunomodulation; Macrophages; Male; Mice; Mice, Inbred CBA; Morphine; Nitric Oxide; Oxycodone; Reactive Oxygen Species

Topics: Administration, Oral; Analgesics, Opioid; Buprenorphine; Dermatitis, Allergic Contact; Dermatitis, Contact; Female; Humans; Middle Aged; Patch Tests; Tramadol

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Dermatitis, Allergic Contact; Dermatitis, Contact; Female; Humans; Middle Aged; Tramadol

Previous research has demonstrated that, in male rats, the magnitude of contact hypersensitivity (CHS) can be enhanced by morphine treatment. The present experiments test the hypothesis that the mu-opioids morphine, etorphine, and buprenorphine would produce significant sex differences in the magnitude of 2,4-dinitrofluorobenzene-induced CHS. During tests conducted over a 192-h period, morphine, etorphine, and buprenorphine administered before elicitation of CHS on the external surface of the ear (pinna) potentiated the CHS response, and the magnitude of this enhancement was significantly greater in females than males. By contrast, morphine had no effect on croton oil-induced irritant contact dermatitis, indicating that morphine's effects on CHS do not generalize to immunologically nonspecific forms of contact dermatitis. Activation of brain mu-opioid receptors is responsible for the effects of morphine on CHS, because intracerebroventricular treatment with the mu-opioid receptor antagonist beta-funaltrexamine blocked morphine potentiation of CHS in females and males. The sex differences in morphine potentiation of CHS appear to be a result of the gonadal hormonal milieu, because castration enhanced the CHS response following vehicle and morphine treatment, whereas ovariectomy significantly attenuated the enhancement of CHS by morphine. Because ovariectomy had no effect on the CHS response following vehicle treatment, the presence of female gonadal hormones may underlie the sex differences in morphine potentiation of CHS in gonadally intact animals. Overall, these results support an increased sensitivity to the modulatory effects of opioids on the CHS response in females that depends on the interaction between gonadal hormones and the central mu-opioid system.

Topics: Animals; Buprenorphine; Castration; Dermatitis, Contact; Etorphine; Female; Gonadal Steroid Hormones; Male; Morphine; Naltrexone; Rats; Rats, Inbred F344; Receptors, Opioid, mu; Sex Characteristics