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Endomorphins and ohmefentanyl in the inhibition of immunosuppressant function in rat peritoneal macrophages: An
Wei-Yan Li1, Jian-Jun Yang1, Si-Hai Zhu1
1Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
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.
Insights
Endomorphins (EMs) and ohmefentanyl (OMF) were found to suppress the immune function of rat macrophages in vitro. These opioids decreased pro-inflammatory cytokine production and impaired macrophage phagocytic and bactericidal activities.
Area of Science:
- Immunology
- Pharmacology
- Cell Biology
Background:
- Opioids may possess immunosuppressant properties with clinical relevance.
- The impact of endomorphins (EMs) and ohmefentanyl (OMF) on rat peritoneal macrophages is not well understood.
Purpose of the Study:
- To investigate the in vitro immunosuppressant effects of EMs and OMF on cultured rat peritoneal macrophages.
Main Methods:
- Cultured rat peritoneal macrophages were treated with EM-1, EM-2, OMF, or saline.
- Measured concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β).
- Assessed macrophage phagocytic and bactericidal activities.
Main Results:
- EM-1, EM-2, and OMF significantly decreased TNF-α and IL-1β concentrations in a time- and dose-dependent manner.
- Macrophage phagocytic and bactericidal activities were significantly reduced by EM-1, EM-2, and OMF.
- All tested substances showed significant immunosuppressive effects compared to saline control.
Conclusions:
- Endomorphins (EMs) and ohmefentanyl (OMF) inhibit the function of cultured rat peritoneal macrophages in vitro.
- These opioids reduce pro-inflammatory cytokine release and impair macrophage immune functions.
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