Skip to main content

Advertisement

SpringerLink
Log in

Morphine, but Not Ketamine, Decreases the Ratio of Th1/Th2 in CD4-positive Cells Through T-bet and GATA3

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

This study was conducted to investigate the effect of morphine on CD4-positive T cells differentiation and the transcriptional factors induced by phorbol myristate acetate (PMA) and ionomycin. CD4-positive lymphocytes separated from healthy volunteers were incubated by PMA (25 ng/ml) + ionomycin (1 μg/ml) with or without the presence of morphine, ketamine, or naloxone. Th subsets, supernatant cytokines, and transcriptional factors were detected 4 h later. Th1 and Th2 cells, levels of INF-γ, IL-2, IL-4 and the activities of T-bet and GATA3 were significantly increased after incubation with PMA and ionomycin. However, the number of Th1 cells, Th1/ Th2, the levels of INF-γ and INF-γ/IL-4, and the activities and protein levels of T-bet and GATA3 were decreased after incubation with PMA and ionomycin in the presence of morphine. Naloxone can abolish morphine’s suppressive effect on Th cell differentiation. Morphine has a negative effect on Th cell balance induced by PMA and ionomycin, the mechanism is related to T-bet and GATA3.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

REFERENCES

  1. Kennedy, R., and E. Celis. 2008. Multiple roles for CD4 positive T cells in anti-tumor immune responses. Immunological Reviews 222: 129–144.

    Article  PubMed  CAS  Google Scholar 

  2. Knutson, K.L., and M.L. Disis. 2005. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunological Immunotherapy 54: 721–728.

    Article  CAS  Google Scholar 

  3. De Monte, L., M. Reni, E. Tassi, et al. 2011. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. The Journal of Experimental Medicine 208: 469–478.

    Article  PubMed  Google Scholar 

  4. Tosolini, M., A. Kirilovsky, B. Mlecnik, et al. 2011. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Research 71: 1263–1271.

    Article  PubMed  CAS  Google Scholar 

  5. Ubukata, H., G. Motohashi, T. Tabuchi, et al. 2010. Evaluations of interferon-γ/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients. Journal of Surgical Oncology 102: 742–747.

    Article  PubMed  Google Scholar 

  6. Hong, S., J. Qian, J. Yang, H. Li, L.W. Kwak, and Q. Yi. 2008. Roles of idiotype-specific t cells in myeloma cell growth and survival: Th1 and CTL cells are tumoricidal while Th2 cells promote tumor growth. Cancer Research 68: 8456–8464.

    Article  PubMed  CAS  Google Scholar 

  7. van Sandick, J.W., M.A. Boermeester, S.S. Gisbertz, I.J. ten Berge, T.A. Out, T.C. van der Pouw Kraan, and J.J. van Lanschot. 2003. Lymphocyte subsets and T(h)1/T(h)2 immune responses in patients with adenocarcinoma of the oesophagus or oesophagogastric junction: Relation to pTNM stage and clinical outcome. Cancer Immunological Immunotherapy 52: 617–624.

    Article  Google Scholar 

  8. O’Garra, A., and N. Arai. 2000. The molecular basis of T helper 1 and T helper 2 cell differentiation. Trends in Cellular Biology 10: 542–50.

    Article  Google Scholar 

  9. Zheng, W., and R.A. Flavell. 1997. Transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene in CD4 + T cells. Cell 89: 587–96.

    Article  PubMed  CAS  Google Scholar 

  10. Ji, N., R.A. Sosa, and T.G. Forsthuber. 2011. More than just a T-box: The role of T-bet as a possible biomarker and therapeutic target in autoimmune diseases. Immunotherapy 3: 435–441.

    Article  PubMed  CAS  Google Scholar 

  11. Chazan, S., I. Buda, N. Nesher, et al. 2010. Low-dose ketaminer via intravenous patient-controlled analgesia device after vaious transthoracic procedures improves analgesia and patient and family satisfaction. Pain Management Nursing 11: 169–176.

    Article  PubMed  Google Scholar 

  12. Jackson, K., M. Ashby, D. Howell, et al. 2010. The effectiveness and adverse effects profile of “burst” ketamine in refractory cancer pain: The VCOG PM 1–00 study. Journal of Palliative Care 26: 176–83.

    PubMed  Google Scholar 

  13. Gao M, Jin W, Qian Y, Ji L, Feng G, Sun J. Effect of N-methyl-d-aspartate receptor antagonist on T helper cell differentiation induced by phorbol-myristate-acetate and ionomycin. Cytokine 2011 Jul 25.

  14. Sacerdote, P., L. Gaspani, and A.E. Panerai. 2000. The opioids antagonist naloxone induces a shift from type 2 to type 1 cytokine pattern in normal and shin-grafted mice. Annals of the New York Academy of Sciences 917: 755–763.

    Article  PubMed  CAS  Google Scholar 

  15. Domino, E.F., E.K. Zsigmond, L.E. Domino, et al. 1982. Plasma levels of ketamine and two of its metabolites in surgical patients using a gas chromatographic mass fragmento-graphic assay. Anesthesia and Analgesia 61: 87–92.

    Article  PubMed  CAS  Google Scholar 

  16. Xie, H., X. Wang, G. Liu, and G. Wang. 2003. Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously. The Clinical Journal of Pain 19(5): 317–322.

    Article  PubMed  Google Scholar 

  17. Clements, J.A., W.S. Nimmo, and I.S. Grant. 1982. Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. Journal of Pharmalogical Sciences 71(5): 539–542.

    Article  CAS  Google Scholar 

  18. Hammoud, H.A., G. Aymard, P. Lechat, N. Boccheciampe, B. Riou, and F. Aubrun. 2011. Relationships between plasma concentrations of morphine, morphine-3-glucuronide, morphine-6-glucuronide, and intravenous morphine titration outcomes in the postoperative period. Fundamental and Clinical Pharmacology 25(4): 518–527.

    Article  PubMed  CAS  Google Scholar 

  19. Greeneltch, K.M., A.E. Kelly-Welch, Y. Shi, and A.D. Keegan. 2005. Chronic morphine treatment promotes specific Th2 cytokine production by murine T cells in vitro via a Fas/Fas ligand-dependent mechanism. Journal of Immunology 175(8): 4999–5005.

    CAS  Google Scholar 

  20. Kirchmayer U, Davoli M, Verster A. Naltrexone maintenance treatment for opioid dependence. Cochrane Database System Review 2003; 2:CD001333.

    Google Scholar 

  21. Giacomelli, R., P. Cipriani, M. Matucci Cerinic, A. Fulminis, G. Barattelli, E. Pingiotti, M. Di Franco, A. Trotta, R. Perricone, F. Zazzeroni, E. Alesse, and G. Tonietti. 2002. Combination therapy with cyclosporine and methotrexate in patients with early rheumatoid arthritis soon inhibits TNFalpha production without decreasing TNFalpha mRNA levels. An in vivo and in vitro study. Clinical and Experimental Rheumatology 20(3): 365–372.

    PubMed  CAS  Google Scholar 

  22. Hackstein, H., J. Misterek, A. Nockher, A. Reiter, G. Bein, and W. Woessmann. 2009. Mini buffy coat photopheresis for children and critically ill patients with extracorporeal photopheresis contraindications. Transfusion 49(11): 2366–2373.

    Article  PubMed  Google Scholar 

  23. Okuno, K., K. Taya, C.R. Marmarou, P. Ozisik, G. Fazzina, A. Kleindienst, S. Gulsen, and A. Marmarou. 2008. The modulation of aquaporin-4 by using PKC-activator (phorbol myristate acetate) and V1a receptor antagonist (SR49059) following middle cerebral artery occlusion/reperfusion in the rat. Acta Neurochirurgia Suppl. 102: 431–436.

    Article  Google Scholar 

  24. Liu, Q.G., D.L. Yang, Y. Huang, E.L. Jiang, S.Y. Zhou, Y. He, Z.D. Wang, M. Wang, Z. Zhou, W.J. Zai, S.Z. Feng, and M.Z. Han. 2006. Influence of G-CSF mobilization on functions of donor T lymphocyte subpopulation and acute graft-versus-host disease. Zhongguo Shi Yan Xue Ye Xue Za Zhi 14(1): 107–111.

    PubMed  CAS  Google Scholar 

  25. Braun, S., N. Gaza, R. Werdehausen, H. Hermanns, I. Bauer, M.E. Durieux, M.W. Hollmann, and M.F. Stevens. 2010. Ketamine induces apoptosis via the mitochondrial pathway in human lymphocytes and neuronal cells. British Journal of Anaesthesia 105: 347–354.

    Article  PubMed  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

We thank Genbao Feng, Jinling hospital, Nanjing, Jiangsu province, China for his technical assistance. The study was supported by National Natural Science Foundation of China (30801068).

Author information

Authors and Affiliations

  1. Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, China

    Mei Gao, Jie Sun, Wenjie Jin & Yanning Qian

Authors
  1. Mei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wenjie Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanning Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yanning Qian.

Additional information

Sun and Gao are co-first author and contributed equally to this paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gao, M., Sun, J., Jin, W. et al. Morphine, but Not Ketamine, Decreases the Ratio of Th1/Th2 in CD4-positive Cells Through T-bet and GATA3. Inflammation 35, 1069–1077 (2012). https://doi.org/10.1007/s10753-011-9413-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-011-9413-6

KEY WORDS

Search

Navigation