BACKGROUND: The potential immunosuppressant effects of opioids might have clinical implications. The effects of endomorphins (EMs) and ohmefentanyl (OMF) on cultured rat peritoneal macrophages remain unclear. OBJECTIVE: The aim of this study was to investigate the immunosuppressant effects of EMs and OMF on cultured rat peritoneal macrophages in vitro. METHODS: Purified rat peritoneal macrophages, from healthy adult male Sprague-Dawley rats, were cultured with EM-1 (EM-1 group), EM-2 (EM-2 group), OMF (OMF group), and saline (saline group). We measured the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-β in supernatant when macrophages were cultured with 10(-6) mol/L of EM-1, EM-2, OMF, or saline for 0, 6, 12, and 24 hours (time-effect relationship) or with 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L of these substances for 24 hours (concentration-effect relationship). We also determined the phagocytic and bactericidal activities of macrophages using isotope markers when macrophages were cultured with 10(-6) mol/L of EM-1, EM-2, OMF, or saline for 24 hours. RESULTS: Compared with the saline group, TNF-α concentration decreased significantly in the OMF, EM-2, and EM-1 groups at 12 hours (P < 0.05, P < 0.05, and P < 0.01, respectively) and at 24 hours (P < 0.05, P < 0.01, and P < 0.01, respectively). Compared with the saline group, IL-1β concentration decreased signifcantly in the OMF, EM-2, and EM-1 groups at 12 hours (P < 0.05, P < 0.05, and P < 0.01, respectively) and at 24 hours (P < 0.05, P < 0.01, and P < 0.01, respectively). Decreased TNF-α and IL-1β concentrations were observed in the supernatant at 24 hours when cultured with 10(-8), 10(-7), and 10(-6) mol/L in the OMF and EM-2 groups (all, P < 0.05) and in the EM-1 group (all, P < 0.01). Compared with the saline group, macrophage phagocytic activity (all, P < 0.05) and macrophage bactericidal activity (all, P < 0.01) were significantly lower in the 3 experimental groups compared with the saline group. CONCLUSION: In this in vitro experiment, EM-1, EM-2, and OMF inhibited the immunosuppressant function of cultured rat peritoneal macrophages, including decreasing TNF-α and IL-1β concentrations and phagocytic and bactericidal activities.
BACKGROUND: The potential immunosuppressant effects of opioids might have clinical implications. The effects of endomorphins (EMs) and ohmefentanyl (OMF) on cultured rat peritoneal macrophages remain unclear. OBJECTIVE: The aim of this study was to investigate the immunosuppressant effects of EMs and OMF on cultured rat peritoneal macrophages in vitro. METHODS: Purified rat peritoneal macrophages, from healthy adult male Sprague-Dawley rats, were cultured with EM-1 (EM-1 group), EM-2 (EM-2 group), OMF (OMF group), and saline (saline group). We measured the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-β in supernatant when macrophages were cultured with 10(-6) mol/L of EM-1, EM-2, OMF, or saline for 0, 6, 12, and 24 hours (time-effect relationship) or with 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L of these substances for 24 hours (concentration-effect relationship). We also determined the phagocytic and bactericidal activities of macrophages using isotope markers when macrophages were cultured with 10(-6) mol/L of EM-1, EM-2, OMF, or saline for 24 hours. RESULTS: Compared with the saline group, TNF-α concentration decreased significantly in the OMF, EM-2, and EM-1 groups at 12 hours (P < 0.05, P < 0.05, and P < 0.01, respectively) and at 24 hours (P < 0.05, P < 0.01, and P < 0.01, respectively). Compared with the saline group, IL-1β concentration decreased signifcantly in the OMF, EM-2, and EM-1 groups at 12 hours (P < 0.05, P < 0.05, and P < 0.01, respectively) and at 24 hours (P < 0.05, P < 0.01, and P < 0.01, respectively). Decreased TNF-α and IL-1β concentrations were observed in the supernatant at 24 hours when cultured with 10(-8), 10(-7), and 10(-6) mol/L in the OMF and EM-2 groups (all, P < 0.05) and in the EM-1 group (all, P < 0.01). Compared with the saline group, macrophage phagocytic activity (all, P < 0.05) and macrophage bactericidal activity (all, P < 0.01) were significantly lower in the 3 experimental groups compared with the saline group. CONCLUSION: In this in vitro experiment, EM-1, EM-2, and OMF inhibited the immunosuppressant function of cultured rat peritoneal macrophages, including decreasing TNF-α and IL-1β concentrations and phagocytic and bactericidal activities.
Authors: Robert E Gawley; Mykhaylo Dukh; Claudia M Cardona; Stephan H Jannach; Denise Greathouse Journal: Org Lett Date: 2005-07-07 Impact factor: 6.005