Influence of β-endorphin on phytohemagglutinin-induced lymphocyte proliferation and on the expression of mononuclear cell surface antigens in vitro

Recent evidence suggests that opiates can modulate the immune responses. In particular it has been shown that β-endorphin and morphine are able to depress some T lymphocyte functions in humans. In the present study, experiments were designed to evaluate the effect of β-endorphin phytohemagglutinin-induced lymphocyte proliferation and determine the mechanism of this action. The ability of naloxone to block the effect of β-endorphin was also investigated, and the influence of β-endorphin on the expression of mononuclear cell surface antigens using the OKT3, OKT4, OKT8, anti-HLA-DR and anti-β₂-microglobulin monoclonal antibodies was evaluated. Phytohemagglutinin-induced lymphocyte proliferation was significantly inhibited by β-endorphin. This effect occurred when β-endorphin was added to cells at the beginning of the culture period (30 min before, simultaneously or 30 min after phytohemagglutinin), but not when added after 48 h of incubation. The preincubation of cells with BEP for 1 h, 4 h or 24 h did not affect lymphocyte activation by phytohemagglutinin. A ten-fold excess of naloxone, added to cultures 30 min prior to β-endorphin, did not block the inhibitory effect. Incubation with β-endorphin had different effects on each surface antigen tested. The OKT8⁺ and β₂-microglobulin⁺ cells did not show significant variations. The OKT4⁺ cells significantly decreased, after 4 h of incubation with β-endorphin, both in mononuclear cell and in purified T lymphocyte cultures and, after 24 h, in mononuclear cell cultures only. The OKT3⁺ cells decreased, in mononuclear cell cultures only, after 24 h β-endorphin incubation. The HLA-DR⁺ cells significantly increased after a 24 hr incubation period with β-endorphin in mononuclear cell cultures. These results demonstrate that β-endorphin inhibits phytohemagglutinin-induced lymphocyte proliferation, enhances the expression of HLA-DR antigen in mononuclear cells and reduces the expression of T3 and T4 antigens in T lymphocytes.