Effects of morphine, fentanyl and tramadol on human immune response

  • Liu Zhihen  (刘志恒)
  • Gao Feng  (高峰)
  • Tian Yuke  (田玉科)


Morphine has been reported to suppress human immune response. We aimed to observe the effects of morphine, fentanyl and tramadol on NF-κB 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-κB 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-κB 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-κB. Fentanyl had different effects on human immune response in vitro and in vivo. Tramadol may have immune enhancing effect.

Key words

morphine fentanyl tramadol NF-κB IL-2 


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  1. 1.
    Malik A A, Radhakrishnan N, Reddy K et al. Morphine-induced macrophage apoptosis modulates migration of macrophages: use of in vitro model of urinary tract infection. J Endourol, 2002,16(8):605–610PubMedCrossRefGoogle Scholar
  2. 2.
    Gaveriaux-Ruff C, Matthes H W, Peluso J et al. Abolition of morphine-immunosuppression in mice lacking the mu-opioid receptor gene. Proc Natl Acad Sci U S A. 1998, 26;95(11):6326–6330PubMedCrossRefGoogle Scholar
  3. 3.
    Pahl H L. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene, 1999, 22:18(49):6853–6866PubMedCrossRefGoogle Scholar
  4. 4.
    Loop T, Liu Z, Humar M et al. Thiopental inhibits the activation of nuclear factor kappaB. Anesthesiology. 2002 May;96(5):1202–1213PubMedCrossRefGoogle Scholar
  5. 5.
    Roy S, Cain K J, Chapin R B et al. Morphine modulates NF kappa B activation in macrophages. Biochem Biophys Res Commun, 1998,245(2):392–6PubMedCrossRefGoogle Scholar
  6. 6.
    Welters I D, Menzebach A, Goumon Y et al. Morphine inhibits NF-kappaB nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism. Anesthesiology, 2000,92(6):1677–84PubMedCrossRefGoogle Scholar
  7. 7.
    Ghosh S. Regulation of inducible gene expression by the transcription factor NF-kappaB. Immunol Res, 1999, 19(2–3):183–9PubMedGoogle Scholar
  8. 8.
    Yamamoto Y, Gaynor R B. Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J Clin Invest, 2001,107(2):135–42PubMedCrossRefGoogle Scholar
  9. 9.
    House R V, Thomas P T, Bhargava H N. In vitro evaluation of fentanyl and meperidine for immunomodulatory activity. Immunol Lett, 1995,46(1–2):117–24PubMedCrossRefGoogle Scholar
  10. 10.
    Yeager M P, Procopio M A, DeLeo J A et al. Intravenous fentanyl increases natural killer cell cytotoxicity and circulating CD16(+) lymphocytes in humans. Anesth Analg, 2002,94(1):94–9PubMedCrossRefGoogle Scholar
  11. 11.
    Magrini M, Rivolta G, Bolis C et al. Analgesic activity of tramadol and pentazocine in postoperative pain. Int J Clin Pharmacol Res. 1998;18(2):87–92PubMedGoogle Scholar
  12. 12.
    Sacerdote P, Bianchi M, Manfredi B et al. Efects of tramadol on immune responses and nociceptive thresholds in mice. Pain, 1997,72:325–330PubMedCrossRefGoogle Scholar
  13. 13.
    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(6):1411–4PubMedCrossRefGoogle Scholar
  14. 14.
    Livnat S, Felten S Y, Carlson S L et al. Involvement of peripheral and central catecholamine systems in neural-immune interactions. J Neuroimmunol, 1985, 10(1):5–30PubMedCrossRefGoogle Scholar
  15. 15.
    Madden K S, Moynihan J A, Brenner G J et al. Sympathetic nervous system modulation of the immune system. III. Alterations in T and B cell proliferation and differentiation in vitro following chemical sympathectomy. J Neuroimmunol, 1994,49(1–2):77–87PubMedCrossRefGoogle Scholar
  16. 16.
    Taub D D, Eisenstein T K, Geller E B et al. Immunomodulatory activity of mu-and kappa-selective opioid agonists. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):360–4.avio N, Lai M M C. The hepatitis C virus persistence: how to evade the immune system? J Biosci, 2003, 28:287–304PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology 2006

Authors and Affiliations

  • Liu Zhihen  (刘志恒)
    • 1
    • 2
  • Gao Feng  (高峰)
    • 1
  • Tian Yuke  (田玉科)
    • 1
  1. 1.Department of Anesthesiology, Tongji HospitalHuazhong University of Science and TechnologyWuhanChina
  2. 2.Department of AnesthesiologyThe Second Hospital in ShenzhenShenzhenChina

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