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Leu-enkephalin enhances interferon secretion in mice

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Research in Experimental Medicine

Abstract

This work has explored the possibility that alterations of NK activity induced by the opioid pentapeptide leu-enkephalin (LENK) may reflect the alterations in secretion of IFN, an important regulator of NK activity. The NK activity in the spleen of mice was determined in parallel with the plasma IFN level 24 and 48h after an i. p. injection of LENK (10 mg/kg). A known inducer of IFN secretion, polyinosinic-polycytidylic acid (poly-IC), was also used. LENK injection significantly increased basal IFN secretion 24 and 48h later. The level was comparable to that induced by poly-IC. However, LENK was not able to augment the poly-IC-increased IFN level. The increase of IFN at 48 h coincided with a mild enhancement of NK activity in the spleens, but 24 h after LENK injection, the increased IFN level in plasma was associated with a significant drop of splenic NK activity. LENK did not affect the NK activity stimulated with poly-IC. Naloxone (20 mg/kg), an opioid receptor-blocking agent, only partly diminished the LENK-induced IFN secretion. However, naloxone itself increased the plasma IFN level. These data indicate that the immunomodulatory effects of the opioid peptide LENK in vivo are associated with alterations of IFN secretion.

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References

  1. Apte RN, Durum SK, Oppenheim JJ (1990) Opioids modulate interleukin-1 production and secretion by bone-marrow macrophages. Immunol Lett 24:141–148

    Article  PubMed  CAS  Google Scholar 

  2. Carr DJJ, Kim CH, DeCosta B, Jacobson AE, Rice KC, Blalock JE (1988) Evidence for a δ-class opioid receptor on cells of the immun system. Cell Immunol 116:44–51

    Article  PubMed  CAS  Google Scholar 

  3. Brown SL, Epps DE van (1985) Suppression of T lymphocyte chemotactic factor production by the opioid peptide β-endorphin and met-enkephalin. J Immunol 134:3384–3390

    PubMed  CAS  Google Scholar 

  4. Brown SL, Epps DE van (1986) Opioid peptides modulate production of interferon ψ by human mononuclear cells. Cell Immunol 103:19–26

    Article  PubMed  CAS  Google Scholar 

  5. Brummit CF, Sharp BM, Gekker G, Keane WF, Peterson PF (1988) Modulatory effects of β-endorphin on interferon-ψ production by cultured peripheral blood mononuclear cells: heterogeneity among donors and the influence of cultured medium. Brain Behav Immun 2:187–198

    Article  Google Scholar 

  6. Faith RE, Murgo AJ (1988) Inhibition of pulmonary metastases and enhancement of natural killer cell activity by methionine-enkephalin. Brain Behav Immun 2:114–122

    Article  PubMed  CAS  Google Scholar 

  7. Foris G, Medgyesi GA, Hack M (1986) Bidirectional effect of met-enkephalin on macrophage effector functions. Mol Cell Biochem 69:127–137

    Article  PubMed  CAS  Google Scholar 

  8. Forti RL, Moldovan RA, Mitchell WM, Callicoat P, Schuffman SS, Davies HA, Smith DM (1985) Application of an objective biological assay of human interferons to clinical specimens and a survey of a normal population. J Clin Microbiol 21:689–693

    PubMed  CAS  Google Scholar 

  9. Gabrilovac J, Martin-Kleiner I, Osmak M (1990) Modulation of NK and ADCC activities by leu-enkephalin in vivo and in vitro. Period Biol 92:79–81

    Google Scholar 

  10. Gabrilovac J, Antica M, Osmak M (1992) In vivo bidirectional regulation of mouse natural killer (NK) cell cytotoxic activities by leu-enkephalin: reversibility by naloxone. Life Sci 50:29–37

    Article  PubMed  CAS  Google Scholar 

  11. Gabrilovac J, Martin-Kleiner I, Ikic-Sutlic M, Osmak M (1992) Interaction of leu-enkephalin and α-interferon in modulation of NK-activity of human peripheral blood lymphocytes. Ann N Y Acad Sci 650:140–145

    Article  PubMed  CAS  Google Scholar 

  12. Gabrilovac J, Martin-Kleiner I, Kummer U, Thierfelder S (1994) Leu-enkephalin modulates proliferative ability and IL-2 secretion of mouse spleen cells. Period Biol 96:273–274 (Abstract)

    Google Scholar 

  13. Hagi K, Uno K, Inaba K, Muramatsu S (1994) Augmenting effects of opioid peptides on murine macrophage activation. J Neuroimmunol 50:71–76

    Article  PubMed  CAS  Google Scholar 

  14. Hucklebridge FH, Hudspith BN, Muhamed J, Lydyard PM, Brostoff J (1989) Methionineenkephalin stimulates in vitro proliferation of human peripheral lymphocytes via δ-opioid receptors. Brain Behav Immun 3:183–189

    Article  PubMed  CAS  Google Scholar 

  15. Jankovic BD, Maric D (1987) Enkephalins and immunity. I. In vivo suppression and potentiation of humoral immune response. Ann N Y Acad Sci 496:115–125

    Article  PubMed  CAS  Google Scholar 

  16. Johnson HM, Smith EM, Torres BA, Blalock (1982) Regulation of the in vitro antibody response by neuroendocrine hormones. Proc. Natl Acad Sci USA 79:4171–4174

    Article  PubMed  CAS  Google Scholar 

  17. Kastin AJ, Seligson J, Strimas JH, Chi DS (1991) Failure of met-enkephalin to enhance natur killer cells. Immunobiology 183:55–68

    PubMed  CAS  Google Scholar 

  18. Kusnecov AW, Husband AJ, King MG, Pang G, Smith R (1987) In vivo effects of β-endorphin on lymphocyte proliferation and interleukin 2 production. Brain Behav Immun 1:88–97

    Article  PubMed  CAS  Google Scholar 

  19. Mandler RN, Biddison WE, Mandler R, Serrate SA (1986) β-endorphin augments the cytolytic activity and interferon production of natural killer cells. J Immunol 136:934–939

    PubMed  CAS  Google Scholar 

  20. Marotti T, Sverko V, Hrsak I (1990) Modulation of superoxide anion release from human polymorphonuclear cells by met- and leu-enkephalin. Brain Behav Immun 4:13–22

    Article  PubMed  CAS  Google Scholar 

  21. Marotti T, Burek B, Rabatic S, Balog T, Hrsak I (1994) Modulation of lipopolysaccharideinduced production of cytokines by methionine-enkephalin. Immunol Lett 40:43–47

    Article  PubMed  CAS  Google Scholar 

  22. Oleson DR, Johnson DR (1988) Regulation of human natural cytotoxicity by enkephalins and selective opiate agonists. Brain Behav Immun 2:171–186

    Article  PubMed  CAS  Google Scholar 

  23. Prete P, Levin ER, Padram A (1986) The in vitro effects of endogenous opiates on natural killer cells, antigen-specific cytolytic T-cells, and T-cell subsets. Exp Neurol 92:349–359

    Article  PubMed  CAS  Google Scholar 

  24. Shavit Y, DePaulis A, Martin FC, Terman GW, Pechnick RN, Zane CJ, Gaele RP, Liebeskind JC (1986) Involvement of brain opiate receptors in the immune-suppressive effect of morphine. Proc Natl Acad Sci USA 83:7114–7117

    Article  PubMed  CAS  Google Scholar 

  25. Bergh P van den, Rozing J, Nagelkerken J (1991) Two opposing modes of action of β-endorphin on lymphocyte function. Immunology 72:537–543

    PubMed  Google Scholar 

  26. Bergh P van den, Dobber R, Ramlal S, Rozing J, Nagelkerken L (1984) Role of opioid peptides in the regulation of cytokine production by murine CD4+ T cells. Cell Immunol 154:109–122

    Article  Google Scholar 

  27. Weigent DA, Blalock JE (1987) Interaction between the neuroendocrine and immune systems: common hormones and receptors. Immunol Rev 100:79–108

    Article  PubMed  CAS  Google Scholar 

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Gabrilovac, J., Ikic-Sutlic, M., Knezevic, N. et al. Leu-enkephalin enhances interferon secretion in mice. Res. Exp. Med. 196, 137–144 (1996). https://doi.org/10.1007/BF02576835

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  • DOI: https://doi.org/10.1007/BF02576835

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