Chronic Morphine Consumption Increase Allograft Rejection Rate in Rat through Inflammatory Reactions

Background: Although opioids suppressive effects on immune system function have been reported, this study demonstrates inflammatory reactions, such as production of pro-inflammatory cytokines and suppression of anti-inflammatory cytokines, are the main causes at organ’s allotransplantation rejection in chronic morphine-treated recipients. Methods: 28 rats were categorized in 4groups through intra-peritoneal administrations: control, sham, morphine treated animals (20 mg/kg injected of morphine daily until biopsy day), morphine and naloxane treated animals (20 mg/kg morphine and 2 mg/kg naloxane daily injected until biopsy day), which their donors were normal rats. The grafts were done at the 14th day of the experiment. Plasma interleukins levels (IL-6 and IL-10) in three sampling times were measured by ELISA. With almost 80% of macroscopic rejection signs in rats of one group, full thickness skin biopsy has been taken and histological parameters like perivascular infiltrates, epidermal changes, and stromal changes were detected. The statistical significance differences between the control and experimental groups were analyzed using the Kruskal-Wallis, followed by ANOVA post hoc test. Results: Accelerated skin allograft rejection by chronic morphine consumption can be resulted of increased IL-6 concentration and decreased IL-10. The enhancing effects of morphine on the graft inflammation were partially antagonized by Naloxane. It can illustrate the complexity of opiates and immune system connections and should be considered during organ transplantation of opiate addicts. Conclusion: Expansion of skin cells in recipient with chronic morphine administration history may be resulted in failure.