Skip to main content
Log in

Agonists of μ- and δ-opioid receptors in the regulation of IL-2, IL-4, and IFN-γ production by peripheral blood cells in vitro

  • Published:
Human Physiology Aims and scope Submit manuscript

Abstract

It was found that β endorphin stimulates the phytohemagglutinin (PHA)-induced production of interleukin-4 (IL-4) and has no effect on the production of interferon-γ in unfractionated leukocyte suspension. In the culture of purified CD4+ T cells, β-endorphin does not affect the concentration of IL-2, IL-4, and IFN-γ but stimulates the production of IL-4 and inhibits the production of IFN-γ when monocytes are added to the culture. Selective δ-agonist DADLE enhances the PHA-induced production of IL-4-in unfractionated leukocyte suspension and in the system containing CD4+ lymphocytes and monocytes. The synthesis of IFN-γ by purified CD4+ lymphocytes is not changed in the presence of DADLE, DAGO, and Deltorphin II; however, when monocytes are added to the culture, the synthesis rate decreases. β-Endorphin and selective μ-agonist DAGO enhance the production of IFN-γ by stimulated neutrophils. The production of IFN-γ by CD8+ lymphocytes is not affected by β-endorphin. Thus, opioid peptides have predominantly a Th2-polarizing effect, which is monocyte-mediated, hindering the development of cell response by inhibiting IFN-γ and stimulating the production of IL-4 by activating δ-receptor. Neutrophils can also enhance the production of IFN-γ by stimulating μ-receptor.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sharp, B.M., Multiple opioid receptors on immune cells modulate intracellular signaling, Brain Behav. Immun., 2006, vol. 20, p. 9.

    Article  CAS  Google Scholar 

  2. Kovalitskaya, Yu.A. and Novolotskaya, E.V., Nonopioid effect of β-endorphin, Biochemistry (Moscow), 2011, vol. 76, no. 4, p. 379.

    CAS  PubMed  Google Scholar 

  3. Bidlack, J.M., Detection and function of opioid receptors on cells from the immune system, Clin. Diagnos. Lab. Immunol., 2000, vol. 7, p. 719.

    CAS  Google Scholar 

  4. Gein, S.V. and Baeva, T.A., Endogenous opioid peptides in regulation of innate immunity cell functions, Biochemistry (Moscow), 2011, vol. 76, no. 3, p. 379.

    Article  Google Scholar 

  5. Bodnar, R.J., Endogenous opiates and behavior: 2012, Peptides, 2013, vol. 50, p. 55.

    Article  CAS  Google Scholar 

  6. Ellis, T.N. and Beaman, B.L., Murine polymorphonuclear neutrophils produce interferon-gamma in response to pulmonary infection with Nocardia asteroids, J. Leukocyte Biol., 2002, vol. 72, p. 373.

    CAS  PubMed  Google Scholar 

  7. Gein, S.V., Baeva, T.A., Gein, O.N., and Chereshnev, V.A., The role of monocytes in the effects of β-endorphin and selective agonists of μ- and δ-opiate receptors on the proliferative activity of peripheral blood lymphocytes, Fiziol. Chel., 2006, vol. 32, no. 3, p. 346.

    CAS  Google Scholar 

  8. Bergh, P., Rosing, J., and Nagelkerken, L., β-endorphin stimulates Ia expression on mouse B cells by inducing interleukin-4 secretion by CD4+ T cells, Cell. Immunol., 1993, vol. 149, p. 180.

    Article  Google Scholar 

  9. Nakae, S., Komiyama, Y., and Yokoyama, H., IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response, Int. Immunol., 2003, vol. 44, p. 483.

    Article  Google Scholar 

  10. Gein, S.V., Gorshkova, K.G., and Tendryakova, S.P., Regulation of IL-1beta and IL-8 production by mu-, delta-opiate receptors agonists in vitro, Ross. Fiziol. Zh. im. I. M. Sechenova, 2008, vol. 94, no. 7, p. 812.

    Google Scholar 

  11. Peterson, P.K., Sharp, B., Gekker, G., et al., Opioidmediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells, J. Clin. Invest., 1987, vol. 80, p. 824.

    Article  CAS  Google Scholar 

  12. Fox, B.S. and Li, T.K., The effect of PGE2 on murine helper-T-cell lymphokines, ImmunoMethods, 1993, vol. 2, p. 255.

    Article  CAS  Google Scholar 

  13. Andrews, D.M., Andoniou, C.E., Fleming, P., et al., The early kinetics of cytomegalovirus-specific CD8+ T-cell responses are not affected by antigen load or the absence of perforin or gamma interferon, J. Virol., 2008, vol. 82, p. 4931.

    Article  CAS  Google Scholar 

  14. Hsueh, C.M., Chen, S.F., Huang, H.J., et al., Activation of mu-opioid receptors are required for the conditioned enhancement of NK cell activity, Brain Res., 1996, vol. 737, p. 263.

    Article  CAS  Google Scholar 

  15. Ho, V.W. and Sly, L.M., Derivation and characterization of murine alternatively activated (M2) macrophages, Methods Mol. Biol., 2009, vol. 531, p. 173.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. V. Gein.

Additional information

Original Russian Text © S.V. Gein, S.P. Tendryakova, 2015, published in Fiziologiya Cheloveka, 2015, Vol. 41, No. 3, pp. 112–117.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gein, S.V., Tendryakova, S.P. Agonists of μ- and δ-opioid receptors in the regulation of IL-2, IL-4, and IFN-γ production by peripheral blood cells in vitro. Hum Physiol 41, 323–327 (2015). https://doi.org/10.1134/S0362119715030056

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0362119715030056

Keywords

Navigation