Effects of morphine, fentanyl and tramadol on human immune response

Abstract

Morphine has been reported to suppress human immune response. We aimed to observe the effects of morphine, fentanyl and tramadol on NF-kappa B and IL-2 from both laboratory and clinical perspective. Jurkat cells were incubated with ten times clinically relevant concentrations of morphine, fentanyl and tramadol before being stimulated with PMA. NF-kappa B binding activity and IL-2 levels were measured. In the clinical study, 150 consenting patients were randomized into 3 groups according to the analgesics used in them, namely, group morphine (M), group fentanyl (F) and group tramadol (T). IL-2 was measured preoperatively and 1, 3 and 24 h after operation. Consequently, NF-kappa B activation was suppressed by morphine and fentanyl but not by tramadol. IL-2 was significantly decreased by morphine and fentanyl but not by tramadol in vitro. In the PCA patients, IL-2 was decreased in group M and increased in group F postoperatively. Whereas in group T, IL-2 was unchanged 1 h after operation but was significantly elevated 3 and 24 h after operation. Our results showed that the inhibition of morphine on IL-2 was most probably related to its suppression on NF-kappa B. Fentanyl had different effects on human immune response in vitro and in vivo. Tramadol may have immune enhancing effect.

The impact of caudally administrated tramadol on immune response and analgesic efficacy for pediatric patients: a comparative randomized clinical trial

“…In our study, there was an increase in the postoperative levels of IL-6, CRP (indicators of acute-phase and inflammatory mediator responses), and cortisol levels, and such increases were significantly less evident in tramadol patients. These results are in agreement with other studies which stated that tramadol could enhance secretion of IL-2 and Natural Killer cell activity [ 13 19 ]. These finding may also be related to the postoperative pain experienced by patients in each group.…”

“…Optimal and longer postoperative pain relief could be an explanation for lower levels of IL-6 within the tramadol group, especially that these types of inflammatory mediators are correlated to the hyperalgesic states [ 20 21 ]. Thus, increased production of pro-inflammatory cytokines may contribute to more severe pain and vice versa [ 19 ]. In a comparative study done by Senel and his colleagues, caudal bupivacaine 0.25% (1 ml/kg) with the addition of Tramadol 1.5 mg/kg has resulted in significantly longer postoperative analgesia duration of 13 ± 2.2 h, and these results agree with our finding [ 21 ].…”

Fentanyl Suppresses the Survival of CD4+ T Cells Isolated from Human Umbilical Cord Blood through Inhibition of IKKs‐mediated NF‐κB Activation

“…The parturition results in tissue injury and triggers inflammation; thus, immune systems play important parts in parturition and post‐partum recovery . In the past two decades, opiate anaesthetics have been reported to exert different regulations on immune systems and contribute to the development of post‐injury immunosuppression . The hypothesis is that opiate anaesthetics might conduct immunoregulatory functions in tissue recovery and inflammation modulation in parturition and post‐partum terms.…”

A preliminary evaluation of the effects of opioids on innate and adaptive human in vitro immune function

“…Codeine has been shown to increase IL-8 and TNF-α production 8. In postoperative studies, morphine has been reported to inhibit IL-2 production, which was unaffected by fentanyl and either unaffected or increased by tramadol 44 45…”