Abstract
Purpose: The effects of morphine on natural killer (NK) cell activity were investigated in patients who underwent hysterectomy.
Methods: Forty patients were divided into four of ten. The groups received intrathecal 0.5 mg morphine (Group IT0.5), intrathecal 0.1 mg morphine (Group IT0.1) or 10 mg morphineiv (Group IV). The remaining ten patients served as controls and received inhalation anesthesia alone (Group C). Blood samples were withdrawn before and two hours after surgery and on postoperative days one and two to determine the blood NK cell activity using a chromium release assay with K562 cells as targets, plasma catecholamines and cortisol levels. The postoperative pain score and side effects were studied in the four groups.
Results: In Group IT0.5, the NK cell activity was lower on postoperative day 1 (23.9±8.4%) than the baseline level (45.7±13%) before surgery, and recovered on postoperative day 2. In Groups IT0.1, C and IV, the NK cell activities showed no significant changes. In all four groups, neither plasma adrenaline nor noradrenaline concentrations changed. In all four groups, the plasma cortisol levels increased after surgery, on postoperative days 1 and 2. The pain score was lower two hours after surgery and on postoperative day 1 in Group IT0.5 than in the other groups.
Conclusion: These results suggest that long-lasting analgesic effects of intrathecal 0.5 mg morphine suppress the immune response following abdominal surgery.
Résumé
Objectif: Les effets de la morphine sur l’activité des cellules tueuses naturelles (NK) a été examinée chez des patientes qui devaient subir une hystérectomie.
Methode: Quarante patientes ont été réparties en quatre groupes de dix. Elles ont reçu 0,5 mg de morphine en administration intrathécale (Groupe IT0,5), ou 0,1 mg de morphine intrathécale (Groupe IT0,1) ou 10 mg de morphineiv (Groupe IV). Les dix dernières patientes ont constitué le groupe témoin et n’ont reçu qu’une anesthésie par inhalation (Groupe T). Les prélèvements sanguins ont eu lieu avant l’intervention et deux heures après, et les premier et deuxième jours postopératoires afin de déterminer l’activité sanguine des cellules NK, en utilisant un dosage de la libération de chrome avec des cellules K562 comme cibles, les niveaux plasmatiques de catécholaminse et de cortisol. Les scores de douleur postopératoire et les effets secondaires ont été étudiés chez toutes les patientes.
Résultats: Dans le Groupe IT0,5, l’activité des cellules NK a été plus faible au premier jour postopératoire (23,984%) qu’au niveau de base (45,713%) déterminé avant l’opération, mais a retrouvé cette valeur au jour 2. Dans les Groupes IT0,1, T et IV, l’activité des cellules NK n’a pas été modifiée de façon significative. Dans les quatre groupes, les concentrations plastmatiques d’adrénaline ou de noradrénaline n’ont pas changé et les niveaux de cortisol plasmatique se sont accrus après l’opération aux jours 1 et 2. Le score de douleur a été plus bas dans le Groupe IT0,5 que dans les autres groupes, deux heures après l’intervention et au jour 1 postopératoire.
Conclusion: Ces résultats suggèrent que les effets analgésiques de longue durée de la morphine à 0,5 mg, en administration intrathécale, suppriment la réponse immune à la suite d’une intervention chirurgicale abdominale.
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References
Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979; 50: 149–51.
Shvit Y, Depaulis A, Martin FC, et al. Involvement of brain opiate receptors in the immune-suppressive effect of morphine. Neurobiology 1986; 83: 7114–7.
Yeager MP, Colacchio TA, Yu CT, et al. Morphine inhibits spontaneous and cytokine-enhanced natural killer cell cytotoxity in volunteers. Anesthesiology 1995; 83: 500–8.
Bryant HU, Bernton EW, Kenner JR, Holaday JW. Role of adrenal cortical activation in the immunosuppressive effects of chronic morphine treatment. Endocrinology 1991; 128: 3253–8.
Hernandez MC, Flores LR, Bayer BM. Immunosuppression by morphine is mediated by central pathways. J Pharmacol Exp Ther 1993; 267: 1336–41.
Arora PK, Fride E, Petitto J, Waggie K, Skolnick P. Morphine-induced immune alterationsin vivo. Cell Immunol 1990; 126: 343–53.
Bussiere JL, Taub DD, Meissler JJ Jr,Adler MW, Rogers TJ, Eisenstein TK. Effects of opioids on murine antibody responses. Advances in the Biosciences 1993; 86: 563–72.
Wyhran J, Appleboom T, Famaey J-P, Govaerts A. Suggestive evidence for receptors for morphine and methionine-enkephalin on normal human blood T lymphocytes. J Immunol 1979; 123: 1068–70.
Mandler RN, Biddison WE, Mandler R, Serrate SA. ß-endorphin augments the cytolytic activity and interferon production of natural killer cells. J Immunol 1986; 136: 934–9.
Kutza J, Gratz I, Afshar M, Murasko DM. The effects of general anesthesia and surgery on basal and interferon stimulated natural killer cell activity of humans. Anesth Analg 1997; 85: 918–23.
Slade MS, Simmons RL, Yunis E, Greenberg LJ. Immunosuppression after major surgery in normal patients. Surgery 1975; 78: 363–72.
Walton B. Effect of anaesthesia and surgery on immune status. Br J Anaesth 1979; 51: 37–43.
Pedersen BK, Beyer JM. Characterization of thein vitro effects of glucocorticoids on NK cell activity. Allergy 1986; 41: 220–4.
Heilig M, Irwin M, Grewal I, Sercarz E. Sympathetic regulation of T-helper cell function. Brain Behav Immun 1993; 7: 154–63.
Griffith CDM, Kamath MB. Effect of halothane and nitrous oxide anaesthesia on natural killer lymphocytes from patients with benign and malignant breast disease. Br J Anaesth 1986; 58: 540–3.
Drasner K, Bernards CM, Ozanne GM. Intrathecal morphine reduces the minimum alveolar concentration of halothane in humans. Anesthesiology 1988; 69: 310–2.
Samii K, Chauvin M, Viars P. Postoperative spinal analgesia with morphine. Br J Anaesth 1981; 53: 817–20.
Bayer BM, Gastongray MR, Hernandez MC. Distinction between the in vitro and in vivo inhibitory effects of morphine on lymphocyte proliferation based on agonist sensitivity and naltrexone reversibility. Immunopharmacology 1992; 23: 117–24.
Hamra JG, Yaksh TL. Equianalgesic doses of subcutaneous but not intrathecal morphine alter phenotypic expression of cell surface markers and mitogen-induced proliferaiton in rat lymphocytes. Anesthesiology 1996; 85: 355–65.
Nelson CJ, Dykstra LA, Lysle DT. Comparison of the time course of morphine’s analgesic and immunologic effects. Anesth Analg 1997; 85: 620–6.
Bromage PR, Camporesi EM, Durant PAC, Nielsen CH. Nonrespiratory side effects of epidural morphine. Anesth Analg 1982; 61: 490–4.
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Yokota, T., Uehara, K. & Nomoto, Y. Intrathecal morphine suppresses NK cell activity following abdominal surgery. Can J Anesth 47, 303–308 (2000). https://doi.org/10.1007/BF03020942
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DOI: https://doi.org/10.1007/BF03020942