IMMUNOLOGICAL ACTION OF [MET(5)]ENKEPHALIN FRAGMENTS

The aim of this study was to evaluate the effects of [Met(5)]enkephali n, des-Met-[Met(5)]enkephalin, des-Tyr-[Met(5)]enkephalin, and Tyr-Gly -Gly on natural killer cytotoxic activity and on concanavalin A- and l ipopolisaccharide-stimulated proliferation of B and T cells in mice. S ingle i.p. injections of [Met(5)]enkephalin, des-Met-[il?et 5]enkephal in, and Tyr-Gly-Gly increased both natural killer cytotoxicity and pro liferation of mitogen-stimulated B and T cells. These effects were inh ibited by naloxone pretreatment, which suggests the opioid mechanism o f the peptides studied. The rate of lymphocytic proliferation increase s not only after single injection of [Met(5)]enkephalin or its metabol ites, but also after 3 or 7 days of treatment. Apart from the function al effects, [Met(5)]enkephalin, des-Met-[Met(5)]enkephalin, and Tyr-Gl y-Gly increased the percentages of natural killer cells and T cells. T he results of this study suggest that the immunomodulatory action of [ Met(5)]enkephalin may be mediated or enhanced by its N-terminal metabo lites des-Met-[Met(5)]enkephalin and Tyr-Gly-Gly. (C) 1998 Elsevier Sc ience B.V.