Immunologic action of [Met5]enkephalin fragments

The aim of this study was to evaluate the effects of [Met5]enkephalin, des-Met-[Met5]enkephalin, des-Tyr-[Met5]enkephalin, and Tyr-Gly-Gly on natural killer cytotoxic activity and on concanavalin A- and lipopolysaccharide-stimulated proliferation of B and T cells in mice. Single i.p. injections of [Met5]enkephalin, des-Met-[Met5]enkephalin, and Tyr-Gly-Gly increased both natural killer cytotoxicity and proliferation of mitogen-stimulated B and T cells. These effects were inhibited by naloxone pretreatment, which suggests the opioid mechanism of the peptides studied. The rate of lymphocytic proliferation increases not only after single injection of [Met5]enkephalin or its metabolites, but also after 3 or 7 days of treatment. Apart from the functional effects, [Met5]enkephalin, des-Met-[Met5]enkephalin, and Tyr-Gly-Gly increased the percentages of natural killer cells and T cells. The results of this study suggest that the immunomodulatory action of [Met5]enkephalin may be mediated or enhanced by its N-terminal metabolites des-Met-[Met5]enkephalin and Tyr-Gly-Gly.