Is immunomodulation by opioid drugs of clinical relevance?

Current Opinion in Anaesthesiology

Volumn 16, Issue 5, 2003, Pages 509-513

  Welters, Ingeborg D ^a  

^a UNIVERSITY HOSPITAL GIESSEN   (Germany)

Author keywords

Chemokine receptor; Immunomodulation; Leukocytes; Morphine; Opioid receptor; Opioids; Receptor crosstalk

Indexed keywords

ANALGESIC AGENT; CHEMOKINE; CHEMOKINE RECEPTOR; KAPPA OPIATE RECEPTOR; MORPHINE; MU OPIATE RECEPTOR; NOCICEPTIN; OPIATE AGONIST; OPIATE RECEPTOR; SIGMA OPIATE RECEPTOR; TRAMADOL;

CLINICAL STUDY; DATA ANALYSIS; DESENSITIZATION; DRUG EFFECT; DRUG MECHANISM; DRUG MEGADOSE; EXPERIMENTATION; HUMAN; IMMUNE SYSTEM; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; LEUKOCYTE; MEDICAL RESEARCH; MOLECULAR MECHANICS; NOCICEPTION; PHOSPHORYLATION; POSTOPERATIVE PAIN; PRIORITY JOURNAL; REVIEW;

EID: 0142124866     PISSN: 09527907     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001503-200310000-00011     Document Type: Review

References (38)

1. Nath A, Hauser KF, Wojna V, et al. Molecular basis for interactions of HIV and drugs of abuse. J Acquir Immune Defic Syndr 2002; 31 (Suppl 2):S62-S69.
2. Asakura H, Watarai M, Shirahata T, Makino S. Viable but nonculturable Salmonella species recovery and systemic infection in morphine-treated mice. J Infect Dis 2002; 186:1526-1529.
3. Kieffer BL, Gaveriaux-Ruff C. Exploring the opioid system by gene knockout. Prog Neurobiol 2002; 66:285-306. Excellent review of the current use of knockout mice, referring to all aspects of opioid receptor actions.
4. Mellon RD, Bayer BM. Evidence for central opioid receptors in the immunomodulatory effects of morphine: review of potential mechanism(s) of action. J Neuroimmunol 1998; 83:19-28.
5. Wang J, Charboneau R, Balasubramanian S, et al. The immunosuppressive effects of chronic morphine treatment are partially dependent on corticosterone and mediated by the mu-opioid receptor. J Leukoc Biol 2002; 71:782-790. Elucidates the direct and indirect actions of morphine on immune function. Although an animal study, new insights into HPA sympathetic nervous system activation can be gained by these experiments.
6. Bhaskaran M, Reddy K, Sharma S, et al. Morphine-induced degradation of the host defense barrier: role of macrophage injury. J Infect Dis 2001; 184:1524-1531.
7. Singhal P, Kapasi A, Reddy K, Franki N. Opiates promote T cell apoptosis through JNK and caspase pathway. Adv Exp Med Biol 2002; 493:127-135. Focuses on opiate-induced apoptosis and pathways involved in this process.
8. 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; 111:139-145.
9. Yeager MP, Yu CT, Campbell AS, et al. Effect of morphine and beta-endorphin on human Fc receptor-dependent and natural killer cell functions. Clin Immunol Immunopathol 1992; 62:336-343.
10. Singhal PC, Sharma P, Kapasi AA, et al. Morphine enhances macrophage apoptosis. J Immunol 1998; 160:1886-1893.
11. Singhal PC, Kapasi AA, Reddy K, et al. Morphine promotes apoptosis in Jurkat cells. J Leukoc Biol 1999; 66:650-658.
12. Flores LR, Dretchen KL, Bayer BM. Potential role of the autonomic nervous system in the immunosuppressive effects of acute morphine administration. Eur J Pharmacol 1996; 318:437-446.
13. Fuertes G, Milanes MV, Rodriguez-Gago M, et al. Changes in hypothalamic paraventricular nucleus catecholaminergic activity after acute and chronic morphine administration. Eur J Pharmacol 2000; 388:49-56.
14. Connor M, Christie MD. Opioid receptor signalling mechanisms. Clin Exp Pharmacol Physiol 1999; 26:493-499.
15. Massotte D, Kieffer BL. A molecular basis for opiate action. Essays Biochem 1998; 33:65-77.
16. Jordan B, Devi LA. Molecular mechanisms of opioid receptor signal transduction. Br J Anaesth 1998; 81:12-19.
17. Grimm MC, Ben Baruch A, Taub DD, et al. Opiates transdeactivate chemokine receptors: delta and mu opiate receptor-mediated heterologous desensitization. J Exp Med 1998; 188:317-325.
18. Onuffer JJ, Horuk R. Chemokines, chemokine receptors and small-molecule antagonists: recent developments. Trends Pharmacol Sci 2002; 23:459-467. Provides an excellent overview of the chemokine network with a special emphasis on the role of chemokines in different diseases.
19. Steele AD, Szabo I, Bednar F, Rogers TJ. Interactions between opioid and chemokine receptors: heterologous desensitization. Cytokine Growth Factor Rev 2002; 13:209-222. Reviews the current ideas of heterologous desensitization. Easy to read, provides insight into the biochemical basics involved in opioid and chemokine receptor crosstalk.
20. Zhang N, Hodge D, Rogers TJ, Oppenheim JJ. Ca2+-independent protein kinase Cs mediate heterologous desensitization of leukocyte chemokine receptors by opioid receptors. J Biol Chem 2003; 278:12729-12736. The most recent work about heterologous desensitization. New mechanisms, especially the impact of calcium-independent protein kinases for opioid receptor mediated desensitization of chemokine receptors. Easy to read, understandable, opening new horizons in opioid-mediated immunomodulation.
21. Suzuki S, Chuang LF, Yau P, et al. Interactions of opioid and chemokine receptors: oligomerization of mu, kappa, and delta with CCR5 on immune cells. Exp Cell Res 2002; 280:192-200. Focuses on co-localization of opioid receptor and CCR5 and its relevance for HIV infection.
22. Szabo I, Chen XH, Xin L, et al. Heterologous desensitization of opioid receptors by chemokines inhibits chemotaxis and enhances the perception of pain. Proc Natl Acad Sci U S A 2002; 99:10276-10281. Possibly the most important paper on the topic. Elucidates how opioid analgesia is reduced after chemokine pretreatment. Convincing animal experiments underline in-vitro findings. Helps us to understand why heterologous desensitization has gained importance during the last year.
23. Mahajan SD, Schwartz SA, Shanahan TC, et al. Morphine regulates gene expression of alpha- and beta-chemokines and their receptors on astroglial cells via the opioid mu receptor. J Immunol 2002; 169:3589-3599.
24. Stefano GB, Goumon Y, Bilfinger TV, et al. Basal nitric oxide limits immune, nervous and cardiovascular excitation: human endothelia express a mu opiate receptor. Prog Neurobiol 2000; 60:513-530.
25. Gavériaux-Ruff C, Matthes HW, Peluso J, Kieffer BL. Abolition of morphine-immunosuppression in mice lacking the mu-opioid receptor gene. Proc Natl Acad Sci U S A 1998; 95:6326-6330.
26. Roy S, Barke RA, Loh HH. μ-Opioid receptor-knockout mice: role of muopioid receptor in morphine mediated immune functions. Brain Res Mol Brain Res 1998; 61:190-194.
27. Holan V, Zajicova A, Krulova M, et al. Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice. Clin Exp Immunol 2003; 132:40-45. Provides interesting insights into modulation of transplant rejection by heroin. Has a strong clinical impact, although conclusions have been driven from animal experiments.
28. Pacifici R, Minetti M, Zuccaro P, Pietraforte D. Morphine affects cytostatic activity of macrophages by the modulation of nitric oxide release. Int J Immunopharmacol 1995; 17:771-777.
29. Peng X, Mosser DM, Adler MW, et al. Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages. J Leukoc Biol 2000; 68:723-728.
30. Houghtling RA, Mellon RD, Tan RJ, Bayer BM. Acute effects of morphine on blood lymphocyte proliferation and plasma IL-6 levels. Ann N Y Acad Sci 2000; 917:771-777.
31. Holan V, Zajicova A, Krulova M, et al. Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice. Clin Exp Immunol 2003; 132:40-45.
32. Limiroli E, Gaspani L, Panerai AE, Sacerdote P. Differential morphine tolerance development in the modulation of macrophage cytokine production in mice. J Leukoc Biol 2002; 72:43-48. Elucidates influence of morphine tolerance on cytokine production. New insights into the complex interaction between chronic and acute morphine treatment on the immune system are demonstrated.
33. Palm S, Lehzen S, Mignat C, et al. Does prolonged oral treatment with sustained-release morphine tablets influence immune function? Anesth Analg 1988; 86:166-172.
34. Page GG. The immune-suppressive effects of pain. Adv Exp Med Biol 2003; 521:117-125.
35. Page GG, Blakely WP, Ben Eliyahu S. Evidence that postoperative pain is a mediator of the tumor-promoting effects of surgery in rats. Pain 2001; 90:191-199.
36. 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; 90:1411-1414.
37. Yokota T, Uehara K, Nomoto Y. Intrathecal morphine suppresses NK cell activity following abdominal surgery. Can J Anaesth 2000; 47:303-308.
38. Gaspani L, Bianchi M, Limiroli E, et al. 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. Exating animal experiments needing confirmation by clinical studies.