Abstract
Purpose
The inhibitory effect of opioids on phagocytic cell capacity is well established. However, the effect of synthetic analgesics on this aspect of cell function is controversial. It was the aim of the study to compare the in vitro effect of tramadol with that of morphine on the engulfing ability of peripheral blood phagocytic cells from healthy volunteers.
Methods
Peripheral blood polymorphonuclear cells and monocytes from healthy volunteers were incubated with 5, 10 and 20 µg·mL-1 tramadol, or with 20, 40 and 80 ng·mL-1 morphine. To each tube, 0.05 mL of 5% suspension of latex beads 0.8 µm in diameter was added. After incubation for 60 min the percentage of cells engulfing latex particles and the phagocytic index (number of particles phagocytized by each individual cell) were detected.
Results
Tramadol affected neither the percentage of cells phagocyting latex particles, nor the phagocytic index of both polymorphonuclear cells and monocytes. On the other hand, incubation with 20, 40 and 80 ng·mL-1 morphine caused 11%, 14% and 24% decrease in phagocytosis (P < 0.01 —P < 0.001). The percentage of monocytes phagocyting latex particles was lower by 16%, 19% and 12% at the three doses tested (P < 0.01 —P < 0.001). The three doses of morphine caused a dose dependent decrease in the monocyte phagocyting index by 20%, 29% and 35.5% respectively (P < 0.05). The polymorphonuclear phagocyting index was not significantly lower following incubation with the drug (P = 0.053).
Conclusion
The lack of noxious effect of tramadol on the engulfing capacity of phagocytic cells suggests additional benefit to the relatively safe profile of the drug.
Résumé
Objectif
Ľeffet inhibiteur des opioïdes sur la capacité des cellules phagocytaires est bien établi. Mais ľeffet des analgésiques synthétiques est controversé. Nous voulions comparer ľeffet in vitro du tramadol et de la morphine sur la capacité ďenglobage que possèdent les cellules sanguines phagocytaires périphériques prélevées chez des volontaires sains.
Méthode
Des polynucléaires et des monocytes ont été prélevés dans le sang périphérique de volontaires sains et incubés avec 5, 10 et 20 µg·mL-1 de tramadol, ou 20, 40 et 80 ng·mL-1 de morphine. À chaque tube, 0,05 mL ďune suspension à 5 % de particules de latex de 0,8 µm de diamètre a été ajouté. Après 60 min ďincubation, le pourcentage de cellules ayant englobé les particules de latex et ľindice phagocytaire (nombre de particules phagocytées par chaque cellule) ont été détectés.
Résultats
Le tramadol n’a pas modifié le pourcentage de cellules qui ont phagocyté les particules de latex, ni ľindice phagocytaire des polynucléaires et des monocytes. Ľincubation avec 20, 40 et 80 ng·mL-1 de morphine a réduit la phagocytose de 11 %, 14 % et 24 % (P < 0,01 — P < 0,001). Le pourcentage de monocytes englobant les particules de latex a baissé de 16 %, 19 % et 12 % pour les trois doses testées (P < 0,01 —P < 0,001). Les trois doses de morphine ont causé une baisse en fonction de la dose de ľindice phagocytaire des monocytes, soit respectivement de 20 %, 29 % et 35,5 % (P < 0,05). Ľindice phagocytaire des polynucléaires n’était pas significativement plus bas à la suite de ľincubation avec le médicament (P = 0,053).
Conclusion
Ľabsence ďeffet nuisible du tramadol sur la capacité des cellules phagocytaires à englober des corps étrangers solides ajoute un avantage possible au profil relativement sécuritaire de ce médicament.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Djaldetti M, Salman H, Bergman M, Djaldetti R, Bessler H. Phagocytosis - the mighty weapon of the silent warriors. Micros Res Tech 2002; 57: 421–31.
Galley HF, DiMatteo MA, Webster NR. Immunomodulation by anaesthetic, sedative and analgesic agents: does it matter? Intensive Care Med 2000; 26: 267–74.
Fricke JR jrJr,Hewitt DJ, Jordan DM, Fisher A, Rosenthal NR. A double-blind placebo-controlled comparison of tramadol/acetaminophen and tramadol in patients with postoperative dental pain. Pain 2004; 109: 250–7.
Duthie DJ. Remifentanil and tramadol. Br J Anaesth 1998; 81: 51–7.
Shipton EA. Tramadol-present and future. Anaesth Intensive Care 2000; 28: 363–74.
Szabo I, Rojavin M, Bussiere JL, Eisenstein TK, Adler MW, Rogers TJ. Suppression of peritoneal macrophage phagocytosis of Candida albicans by opioids. J Pharmacol Exp Ther 1993; 267: 703–6.
Rojavin M, Szabo I, Bussiere JL, Rogers TJ, Adler MW, Eisenstein TK. Morphine treatment in vitro or in vivo decreases phagocytic functions of murine macrophages. Life Sci 1993; 53: 997–1006.
Hamra JG, Yaksh TL. Equianalgesic doses of subcutaneous but not intrathecal morphine alter phenotypic expression of cell surface markers and mitogen-induced proliferation of rat lymphocytes. Anesthesiology 1996; 85: 355–65.
Eisenstein TK, Hilburger ME. Opioid modulation of immune responses: effects on phagocyte and lymphoid cell populations. J Neuroimmunol 1998; 83: 36–44.
Krumholz W, Endrass J, Knecht J, Hempelmann G. The effect of midazolam, droperidol, fentanyl, and alfentanil on phagocytosis and killing of bacteria by polymorphonuclear leukocytes in vitro. Acta Anaesthesiol Scand 1995; 39: 624–7.
Krumholz W, Endrass J, Hempelmann G. Inhibition of phagocytosis and killing of bacteria by anaesthetic agents in vitro. Br J Anaesth 1995; 75: 66–70.
Davidson JA, Boom SJ, Pearsall FJ, Ramsay G. Comparison of the effects of four i.v. anaesthetic agents on polymorphonuclear leucocyte function. Br J Anaesth 1995; 74: 315–8.
Jensen AG, Dahlgren C, Eintrei C. Propofol decreases random and chemotactic stimulated locomotion of human neutrophils in vitro. Br J Anaesth 1993; 70: 99–100.
Sacerdote P, Manfredi B, Mantegazza P, Panerai AE. Antinociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study. Br J Pharmacol 1997; 121: 834–40.
Tomei EZ, Renaud FL. Effect of morphine on Fc-mediated phagocytosis by murine macrophages in vitro. J Neuroimmunol 1997; 74: 111–6.
Welters ID, Menzebach A, Goumon Y, et al. Morphine suppresses complement receptor expression, phagocytosis, and respiratory burst in neutrophils by a nitric oxide and µ3 opiate receptor-dependent mechanism. J Neuroimmunol 2000; 111: 139–45.
Kohnke A, Maier C, Palm S, Barth J. In vitro investigations of the effect of morphine and its metabolites on the phagocytosis of peripheral mononuclear cells (German). Schmerz 1999; 13: 121–6.
Makman MH, Bilfinger TV, Stefano GB. Human granulocytes contain an opiate alkaloid-selective receptor mediating inhibition of cytokine-induced activation and hemotaxis. J Immunol 1995; 154: 1323–30.
Sacerdote P, Bianchi M, Gaspani L, et al. The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients. Anesth Analg 2000; 90: 1411–4.
Pacifici R, Patrini G, Venier I, Parolaro D, Zuccaro P, Gori E. Effect of morphine and methadone acute treatment on immunological activity in mice: pharmaco-kinetic and pharmacodynamic correlates. J Pharmacol Exp Ther 1994; 269: 1112–6.
Alici HA, Ozmen I, Cezur M, Sahin F. Effect of the spinal drug tramadol on the fatty acid compositions of rabbit spinal cord and brain. Biol Pharm Bull 2003; 26: 1403–6.
Sacerdote P, Bianchi M, Manfredi B, Panerai AE. Effects of tramadol on immune responses and nociceptive thresholds in mice. Pain 1997; 72: 325–30.
Gaspani L, Bianchi M, Limiroli E, Panerai AE, Sacerdote P. The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats. J Neuroimmunol 2002; 129: 18–24.
Lazaro MI, Tomassini N, Gonzalez I, Renaud FL. Reversibility of morphine effects on phagocytosis by murine macrophages. Drug Alcohol Depend 2000; 58: 159–64.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Beilin, B., Grinevich, G., Yardeni, I.Z. et al. Tramadol does not impair the phagocytic capacity of human peripheral blood cells. Can J Anesth 52, 1035–1039 (2005). https://doi.org/10.1007/BF03021601
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03021601