Search

The effects of methionine enkephalin (met-enkephalin) on human immune function are reviewed. This pentapeptide functions to upregulate, or enhance, immune function in the majority of donor samples at low doses and suppresses at high doses. The influence of this molecule is shared by the central nervous, neuroendocrine, and immune systems. Cells from each of these systems possess receptors for met-enkephalin and have the ability to process met-enkephalin from its prohormone, proenkephalin A. Studies have shown that this molecule is capable of enhancing immune function in patients with cancer or AIDS. It is proposed that this molecule be classified as a cytokine.

Both methionine enkephalin and leucine enkephalin were found to increase significantly the active T-cell rosettes of normal volunteers. Neither enkephalin altered total T-cell rosettes. It is proposed that the endogenous enkephalins (methionine as well as leucine) have a role in cell-mediated immunity and T-cell function.

Methionine enkephalin was found to increase significantly the active T-cell rosettes from lymphoma patients. In sharp contrast, the leucine enkephalin was observed to increase active rosettes only at a single low concentration. Neither enkephalin significantly altered the total T-cell rosettes. It is suggested that methionine enkephalin could have a significant influence in enhancing cell-mediated immunity and T-cell function, particularly in lymphoma patients.

To further define the effects of enkephalins on immune function, the effect of methionine-enkephalin and leucine-enkephalin on natural killer cell (NK) activity in isolated human peripheral blood lymphocytes was investigated. Incubation of lymphocytes with either enkephalin resulted in significant increases in natural killer cell activity. At effector:target cell ratios of 11:1 methionine-enkephalin significantly (P less than 0.05) enhanced NK activity at dilutions of 10(-6), 10(-8), 10(-10), and 10(-14) mg/ml, while leucine-enkephalin significantly (P less than 0.05) enhanced NK activity at dilutions of 10(-4), 10(-6), 10(-8), 10(-10), and 10(-14) mg/ml. Cells from individuals with low NK activity showed greater percentage increases in NK activity following enkephalin than did cells from individuals with high NK activity.

The subcutaneous injection of either methionine-enkephalin or leucine-enkephalin in BDF1 mice resulted in a significant increase in thymus weight and a significant decrease in spleen weight. This study further supports earlier findings that the enkephalins are neuroimmunomodulators.