Skip to main content
SpringerLink
Log in

Morphine-Induced Enhancement in the Granulocyte Response to Thioglycollate Administration in the Rat

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The present study determined the pharmacological effects of acute morphine treatment on the granulocyte phase of the peritoneal inflammatory response to thioglycollate (TG) in rats. Dual-color flow cytometry using anti-CD11b/c-PE mAb in combination with HIS48-FITC mAb allowed for the determination of morphine's effects on 4 inflammatory cell subsets: CD11b/c+HIS48med granulocytes; CD11b/chiHIS48neg/lo activated macrophages; CD11b/c−HIS48− lymphocytes; and CD11b/c+HIS48hi cells (a monocyte/macrophage and granulocyte subset). Morphine produced a dose-dependent increase in a select subset of inflammatory peritoneal cells, the CD11b/c+HIS48med granulocytes. The effect of morphine was time-dependent, with significant effects first apparent at 4 hr after TG, but the administration of morphine 1 hr before or simultaneously with TG produced a similar increase in CD11b/c+HIS48med granulocytes. Naltrexone completely antagonized the morphine-induced increase in CD11b/c+HIS48med granulocytes. Collectively, these studies show that a single administration of morphine produces a time-dependent, dose-dependent, opioid receptor-mediated enhancement in the peritoneal granulocyte response to TG.

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

Similar content being viewed by others

REFERENCES

  1. Hung, C. Y., S. S. Lefkowitz, and W. F. Geber. 1973. Interferon inhibition by narcotic analgesics. Proc. Soc. Exp. Biol. Med. 142:106–111.

    Google Scholar 

  2. Lefkowitz, S. S. and C. Y. Chiang. 1975. Effects of certain abused drugs on hemolysin forming cells. Life Sci. 17:1763–1768.

    Google Scholar 

  3. Ho, W. K. K. and A. Leung. 1979. The effect of morphine addiction on concanavalin A-mediated blastogenesis. Pharmacol. Res. Comm. 11:413–419.

    Google Scholar 

  4. Güngör, M., E. Genç, H. Sagduyu, L. Eroglu, and H. Koyuncuoglu. 1980. Effect of chronic administration of morphine on primary immune response in mice. Experientia 36:1309–1310.

    Google Scholar 

  5. Tubaro, E., G. Borelli, C. Croce, G. Cavallo, and C. Santiangeli. 1983. Effect of morphine on resistance to infection. J. Infect. Dis. 148:656–666.

    Google Scholar 

  6. Shavit, Y., A. Depaulis, F. C. Martin, G. W. Terman, R. N. Pechnick, C. J. Zane, R. P. Gale, and J. C. Liebeskind. 1986. Involvement of brain opiate receptors in the immune-suppressive effect of morphine. Proc. Natl. Acad. Sci. USA 83:7114–7117.

    Google Scholar 

  7. Hendrickson, M., J. Shelby, J. J. Sullivan, and J. R. Saffle. 1989. Naloxone inhibits the in vivo immunosuppressive effects of morphine and thermal injury in mice. J. Burn Care Rehabil. 10:494–498.

    Google Scholar 

  8. Bayer, B. M., S. Daussin, M. Hernandez, and L. Irvin. 1990. Morphine inhibition of lymphocyte activity is mediated by an opioid dependent mechanism. Neuropharmacol. 29:369–374.

    Google Scholar 

  9. Bryant, H. U. and R. E. Roudebush. 1990. Suppressive effects of morphine pellet implants on in vivo parameters of immune function. J. Pharmacol. Exp. Ther. 255:410–414.

    Google Scholar 

  10. Eisenstein, T. K., J. J. Meissler, Jr., E. B. Geller, and M. W. Adler. 1990. Immunosuppression to tetanus toxoid induced by implanted morphine pellets. Ann. N. Y. Acad. Sci. 594:377–379.

    Google Scholar 

  11. Yeager, M. P., C. T. Yu, A. S. Campbell, M. Moschella, and P. M. Guyre. 1992. Effect of morphine and b-endorphin on human Fc receptor-dependent and natural killer cell functions. Clin. Immunol. Immunopathol. 62:336–343.

    Google Scholar 

  12. Lysle, D. T., M. E. Coussons, V. J. Watts, E. H. Bennett, and L. A. Dykstra. 1993. Morphine-induced alterations of immune status: Dose dependency, compartment specificity and antagonism by naltrexone. J. Pharmacol. Exp. Ther. 265:1071–1078.

    Google Scholar 

  13. Carpenter, G. W., L. Breeden, and D. J. J. Carr. 1995. Acute exposure to morphine suppresses cytotoxic T-lymphocyte activity. Int. J. Immunopharmacol. 17:1001–1006.

    Google Scholar 

  14. Lewis, J. W., Y. Shavit, G. W. Terman, R. P. Gale, and J. C. Liebeskind. 1983 ?1984. Stress and morphine affect survival of rats challenged with a mammary ascites tumor (MAT 13762B). Nat. Immun. Cell Growth Regul. 3:43–50.

    Google Scholar 

  15. Chao, C. C., B. M. Sharp, C. Pomeroy, G. A. Filice, and P. K. Peterson. 1990. Lethality of morphine in mice infected with Toxoplasma gondii. J. Pharmacol. Exp. Ther. 252:605–609.

    Google Scholar 

  16. Ishikawa, M., K. Tanno, A. Kamo, Y. Takayanagi, and K. Sasaki. 1993. Enhancement of tumor growth by morphine and its possible mechanism in mice. Biol. Pharm. Bull. 16:762–766.

    Google Scholar 

  17. Veyries, M.-L., M. Sinet, B. Desforges, and B. Rouveix. 1995. Effects of morphine on the pathogenesis of murine Friend retrovirus infection. J. Pharmacol. Exp. Ther. 272:498–504.

    Google Scholar 

  18. Page, G. G., S. Ben-Eliyahu, and J. C. Liebeskind. 1994. The role of LGL ?NK cells in surgery-induced promotion of metastasis and its attenuation by morphine. Brain Behav. Immun. 8:241–250.

    Google Scholar 

  19. Brown, J. H., J. W. Kissel, and P. M. Lish. 1968. Studies on the acute inflammatory response. I. Involvement of the central nervous system in certain models of inflammation. J. Pharmacol. Exp.Ther. 160:231–242.

    Google Scholar 

  20. Yonehara, N., Y. Iami, and R. Inoki. 1988. Effects of opioids on the heat stimulus-evoked substance P release and thermal edema in the rat hind paw. Eur. J. Pharmacol. 151:381–387.

    Google Scholar 

  21. Joris, J., A. Costello, R. Dubner, and K. M. Hargreaves. 1990. Opiates suppress crrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia. Pain 43:95–103.

    Google Scholar 

  22. Hong, Y. and F. V. Abbott. 1995. Peripheral opioid modulation of pain and inflammation in the formalin test. Eur. J. Pharmacol. 277:21–28.

    Google Scholar 

  23. Nelson, C. J., T. How, and D. T. Lysle. 1999. Enhancement of the contact hypersensitivity reaction by acute morphine administration at the elicitation phase. Clin. Immunol. 93:176–183.

    Google Scholar 

  24. Perrot, S., G. Guilbaud, and V. Kayser. 1999. Effects of intraplantar morphine on paw edema and pain-related behaviour in a rat model of repeated acute inflammation. Pain 83:249–257.

    Google Scholar 

  25. Eisenstein, T. K. and M. E. Hilburger. 1998. Opioid modulation of immune responses: Effects on phagocytic and lymphoid cell populations. J. Neuroimmunol. 83:36–44.

    Google Scholar 

  26. Mellon, R. D. and B. M. Bayer. 1998. Evidence for central opioid receptors in the immunomodulatory effects of morphine: Review of potential mechanism(s) of action. J. Neuroimmunol. 83:19–28.

    Google Scholar 

  27. Glasel, J. A. 2000. The effects of morphine on cell proliferation. Prog. Drug Res. 55:33–80.

    Google Scholar 

  28. Elliott, G. R., M. J. van Batenburg, and M. R. Dzoljic. 1987. Enhanced prostaglandin E2 and thromboxane B2 release from resident peritoneal macrophages isolated from morphine-dependent rats. FEBS Lett. 217:6–10.

    Google Scholar 

  29. Fecho, K., K. A. Maslonek, M. E. Coussons-Read, L. A. Dykstra, and D. T. Lysle. 1994. Macrophage-derived nitric oxide is involved in the depressed concanavalin A responsiveness of splenic lymphocytes from rats administered morphine in vivo. J. Immunol. 152:5845–5852.

    Google Scholar 

  30. Pacifici, R., G. Patrini, I. Venier, D. Parolaro, P. Zuccaro, and E. Gori. 1994. Effect of morphine and methadone acute treatment on immunological activity in mice: Pharmacokinetic and pharmacodynamic correlates. J. Pharmacol. Exp. Ther. 269:1112–1116.

    Google Scholar 

  31. Di Francesco, P., B. Tavazzi, R. Gaziano, G. Lazzarino, I. A. Casalinuovo, D. Di Pierro, and E. Garaci. 1998. Differential effects of acute morphine administrations on polymorphonuclear cell metabolism in various mouse strains. Life Sci. 63:2167–2174.

    Google Scholar 

  32. Chadzinska, M., E. Kolaczkowska, R. Seljelid, and B. Plytycz. 1999. Morphine modulation of peritoneal inflammation in Atlantic salmon and CB6 mice. J. Leukoc. Biol. 65:590–596.

    Google Scholar 

  33. Green, A. P., F. Mangan, and J. E. Ormerod. 1980. Induction of cell infiltration and acid hydrolase release into the peritoneal cavity of mice. Inflammation 4:205–213.

    Google Scholar 

  34. Baron, E. J. and R. A. Proctor. 1982. Elicitation of peritoneal polymorphonuclear neutrophils from mice. J. Immunol. Methods 49:305–313.

    Google Scholar 

  35. Beelen, R. H. J. and W. S. Walker. 1983. Dynamics of cytochemically distinct subpopulations of macrophages in elicited rat peritoneal exudates. Cell. Immunol. 82:246–257.

    Google Scholar 

  36. Qureshi, R. and B. A. Jakschik. 1988. The role of mast cells in thioglycollate-induced inflammation. J. Immunol. 141:2090–2096.

    Google Scholar 

  37. Abe, M., T. Goya, N. Nagata, H. Takahashi, H. Muranishi, and N. Shigematsu. 1992. Time-dependent alterations of leukotriene production and catabolism in rat peritoneal macrophages following intraperitoneal injection of thioglycollate broth. Prostaglandins, Leukotrienes and Essential Fatty Acids 45:59–65.

    Google Scholar 

  38. Kuziel, W. A., S. J. Morgan, T. C. Dawson, S. Griffin, O. Smithies, K. Ley, and N. Maeda. 1997. Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc. Natl. Acad. Sci. USA 94:12053–12058.

    Google Scholar 

  39. Mizgerd, J. P., H. Kubo, G. J. Kutkoski, S. D. Bhagwan, K. Scharffeter-Kochanek, A. L. Beaudet, and C. M. Doerschuk. 1997. Neutrophil emigration in the skin, lungs, and peritoneum: Different requirements for CD11 ?CD18 revealed by CD18-deficient mice. J. Exp. Med. 186:1357–1364.

    Google Scholar 

  40. Robinson, A. P., T. M. White, and D. W. Mason. 1986. Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies, MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunol. 57:239–247.

    Google Scholar 

  41. van Goor, H., V. Fidler, J. J. Weening, and J. Grond. 1991. Determinations of focal and segmental glomerulosclerosis in the rat after renal ablation. Lab. Invest. 64:754–765.

    Google Scholar 

  42. Clark, W. M., J. D. Lauten, N. Lessov, W. Woodward, and B. M. Coull. 1995. Time course of ICAM-1 expression and leukocyte subset infiltration in rat forebrain ischemia. Mol. Chem. Neuropathol. 26:213–230.

    Google Scholar 

  43. Chen, B., T. Chou, and L. Sensenbrenner. 1993. Induction of murine peritoneal macrophage colony-forming cells by peritoneal administration of macrophage inflammatory protein-1. Exp. Hemat. 21:1591–1596.

    Google Scholar 

  44. Rhodes, N. P., J. A. Hunt, and D. F. Williams. 1997. Macrophage subpopulation differentiation by stimulation with biomaterials. J. Biomed. Mater. Res. 37:481–488.

    Google Scholar 

  45. Smith, C. W. 1993. Leukocyte-endothelial cell interactions. Semin. Hematol. 30:45–53.

    Google Scholar 

  46. Fecho, K. and P. L. Cohen. 1998. Fas ligand (gld)-and fas (lpr)-deficient mice do not show alterations in the extravasation or apoptosis of inflammatory neutrophils. J. Leuk. Biol. 64:373–383.

    Google Scholar 

  47. Herz, A. 1995. Role of immune processes in peripheral opioid analgesia. Adv. Exp. Med. Biol. 373:193–199.

    Google Scholar 

  48. Stanfa, L. and A. Dickenson. 1995. Spinal opioid systems in inflammation. Inflammation Res. 44:231–241.

    Google Scholar 

  49. Planas, M. E., L. Rodriguez, S. Sanchez, O. Pol, and M. M. Puig. 1995. Pharmacological evidence for the involvement of the endogenous opioid system in the response to local inflammation in the rat paw. Pain 60:67–71.

    Google Scholar 

  50. Rittner, H. L., A. Brack, H. Machelska, S. A. Mousa, M. Bauer, M. Schäfer, and C. Stein. 2001. Opioid peptide-expressing leukocytes. Anesthesiology 95:500–508.

    Google Scholar 

  51. Simpkins, C. O., C. A. Dickey, and M. P. Fink. 1984. Human neutrophil migration is enhanced by beta-endorphin. Life Sci. 34:2251–2255.

    Google Scholar 

  52. Marcoli, M., G. Ricevuti, A. Mazzone, M. Bekkering, S. Lecchini, and G. M. Frigo. 1988. Opioid-induced modification of granulocyte function. Int. J. Immunopharmacol. 10:425–433.

    Google Scholar 

  53. Grimm, M. C., A. Ben-Baruch, D. D. Taub, O. M. Z. Howard, J. H. Resau, J. M. Wang, H. Ali, R. Richardson, R. Snyderman, and J. J. Oppenheim. 1998. Opiates transdeactivate chemokine receptors: and opiate receptor-mediated heterologous desensitization. J. Exp. Med. 188:317–325.

    Google Scholar 

  54. Kromer, W. 1988. Endogenous and exogenous opioids in the control of gastrointestinal motility and secretion. Pharmacol. Rev. 40:121–162.

    Google Scholar 

  55. Hilburger, M. E., M. W. Adler, A. L. Truant, J. J. Meissler, Jr., V. Satishchandran, T. J. Rogers, and T. K. Eisenstein. 1997. Morphine induces sepsis in mice. J. Infect. Dis. 176:183–188.

    Google Scholar 

  56. Moss, J., N. R. Fahmy, N. Sunder, and M. A. Beaven. 1981. Hormonal and hemodynamic profile of an anaphylactic reaction in man. Circulation 63:210–213.

    Google Scholar 

  57. Rosow, C. E., J. Moss, D. M. Philin, and J. J. Savarese. 1982. Histamine release during morphine and fentanyl anesthesia. Anesthesiology 56:93–96.

    Google Scholar 

  58. Stellato, C., R. Cirillo, A. De Paulis, V. Casolaro, V. Patella, P. Mastronardi, B. Mazzarella, and G. Marone. 1992. Human basophil ?mast cell releasability. IX. Heterogeneity of the effects of opioids on mediator release. Anesthesiology 77:932–940.

    Google Scholar 

  59. Lopker, A., L. G. Abood, W. Hoss, and F. J. Lionetti. 1980. Stereoselective muscarinic acetylcholine and opiate receptors in human phagocytic leukocytes. Biochem. Pharmacol. 29:1361–1365.

    Google Scholar 

  60. Makman, M. H., T. V. Bilfinger, and G. B. Stefano. 1995. Human granulocytes contain an opiate alkaloid-selective receptor mediating inhibition of cytokine-induced activation and chemotaxis. J. Immunol. 154:1323–1330.

    Google Scholar 

  61. Stefano, F. B., P. Melchiorri, L. Negri, T. K. Hughes, Jr., and B. Scharrer. 1992. [D-Ala2]-Deltorphin I binding and pharmaco logical evidence for a special subtype of d opioid receptor on human and invertebrate immune cells. Proc. Natl. Acad. Sci. USA 89:9316–9320.

    Google Scholar 

  62. Magazine, H. I., Y. Liu, T. V. Bilfinger, G. L. Fricchione, and G. B. Stefano. 1996. Morphine-induced conformational changes in human monocytes, granulocytes, and endothelial cells and in invertebrate immunocytes and microglia are mediated by nitric oxide. J. Immunol. 156:4845–4850.

    Google Scholar 

  63. Kolb, H. and V. Kolb-Bachofen. 1992. Nitric oxide: A pathogenetic factor in autoimmunity. Immunol. Today 13:157–160.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology and Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599

    Karamarie Fecho & Donald T. Lysle

  2. Dental Research Center, The University of North Carolina at Chapel Hill, CB #7455, Chapel Hill, North Carolina, 27599-7455

    Karamarie Fecho

Authors
  1. Karamarie Fecho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donald T. Lysle
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fecho, K., Lysle, D.T. Morphine-Induced Enhancement in the Granulocyte Response to Thioglycollate Administration in the Rat. Inflammation 26, 259–271 (2002). https://doi.org/10.1023/A:1021408500630

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021408500630

Search

Navigation