Effect of enkephalins and endorphins on cytotoxic activity of natural killer cells and macrophages/monocytes in mice

Eur J Pharmacol. 1997 May 20;326(2-3):251-5. doi: 10.1016/s0014-2999(97)85420-9.


The effect of [Met5]enkephalin, [Leu5]enkephalin, proenkephalin, dynorphin-(1-17) or beta-endorphin on the cytotoxic (51Cr release assay) activity of natural killer cells and macrophages/monocytes was studied in mice. It was found that a single i.p. injection of [Met5]enkephalin, [Leu5]enkephalin, beta-endorphin, dynorphin or proenkephalin as well as repeated treatment with both enkephalins increased natural killer cell activity. In vitro only [Met5]enkephalin stimulated natural killer cells. Opioid peptides did not affect the cytotoxic activity of macrophages/monocytes. In addition to functional alterations, both enkephalins and beta-endorphin increased the percentage of cells with natural killer phenotype. The results of this study suggest that the increase in natural killer cytotoxicity after opioid peptides injected once or for 14 days may result from an increased number of natural killer cells in the spleen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytotoxicity, Immunologic / drug effects*
  • Drug Evaluation, Preclinical
  • Endorphins / pharmacology*
  • Enkephalins / pharmacology*
  • Female
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / drug effects*
  • Monocytes / immunology


  • Endorphins
  • Enkephalins