Methionine enkephalin (MENK) improves lymphocyte subpopulations in human peripheral blood of 50 cancer patients by inhibiting regulatory T cells (Tregs)

Hum Vaccin Immunother. 2014;10(7):1836-40. doi: 10.4161/hv.28804.


MENK, a penta-peptide is considered as being involved in the regulatory feedback loop between the immune and neuroendocrine systems, with marked modulation of various functions of human immune cells. The aim of the present work was to investigate change of lymphocyte subpopulations in peripheral blood of 50 cancer patients before and after treatment with MENK. Peripheral blood mononuclear cells (PBMCs) of peripheral blood from 50 cancer patients were isolated by density gradient centrifugation using Ficoll-Paque solution and cultured with MENK. We measured proliferation of total nucleated cells, subpopulations of individual CD4+T cells, CD8+T cells, CD4+CD25+ regulatory T cells (Treg), natural killer cells (NK) before and after treatment with 10(-12)M MENK in cell culture by flow cytometry (FCM). Our results indicated that MENK showed a strong inhibiting effect on Treg cells while it stimulated marked proliferation of other lymphocyte subpopulations. All data obtained were of significance statistically. It was therefore concluded that MENK could work as a strong immune booster with great potential in restoring damaged human immune system and we could consider MENK as a drug to treat cancer patients, whose immune systems are damaged by chemotherapy or radiotherapy. Furthermore we could consider MENK as a chemotherapy additive, which would sustain immune system of cancer patients during the process of chemotherapy to get maximized efficacy with minimized side effect.

Keywords: CD4+CD25+ regulatory T cells; CD4+T cell; CD8+T cell; NK; human peripheral blood; lymphocyte subpopulations; methionine enkephalin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Cells
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Enkephalin, Methionine / administration & dosage*
  • Flow Cytometry
  • Humans
  • Immunologic Factors / administration & dosage*
  • Lymphocyte Subsets / immunology*
  • Neoplasms / immunology*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / physiology


  • Immunologic Factors
  • Enkephalin, Methionine