BETA-ENDORPHIN INHIBITS INTERLEUKIN-2 RELEASE AND EXPRESSION OF INTERLEUKIN-2 RECEPTORS IN CONCANAVALIN A-STIMULATED SPLENIC LYMPHOCYTES

Beta-endorphin, when added at the same time as the mitogenic lectin co ncanavalin A to mouse BALB/c spleen lymphocytes, inhibits cell prolife ration. The suppressive effect of beta-endorphin is not exercised thro ugh a cAMP-dependent mechanism and is also observed when splenic lymph ocytes are stimulated with phytohemagglutinin (4 mug/ml), anti-CD3 mon oclonal antibody, or the Ca2+ ionophore A23187 (250 nM) and phorbol 12 -myristate 13-acetate (1 ng/ml). The inhibitory effect of beta-endorph in on lymphocyte proliferation is dose and time dependent: when beta-e ndorphin is added 20 h after Con A stimulation no suppression of lymph ocyte proliferation is observed. Beta-Endorphin inhibits, in a dose-de pendent manner, the release of interleukin-2 in concanavalin A-stimula ted splenic lymphocytes, measured 24 h after stimulation. Beta-Endorph in also controls the appearance of interleukin-2 receptors in the plas ma membrane, but does not regulate the expression of the c-myc protoon cogene. These data indicate that beta-endorphin inhibits lymphocyte ac tivation signal transmission, downstream the generation of the second messengers Ca2+ and diacylglycerol and the expression of the protoonco gene c-myc, by blocking interleukin-2 release and interleukin-2 recept ors expression. Once the cells are in the G1 stage, beta-endorphin is no longer able to block lymphocyte proliferation.