Stimulation of human peripheral lymphocytes by methionine enkephalin and delta-selective opioid analogues

The opioid peptide methionine enkephalin was shown to stimulate human peripheral lymphocyte proliferation in vitro in the absence of mitogen. A study of the time course of stimulation revealed a maximum proliferative response, measured by [3H]thymidine incorporation, after 4-5 days incubation. The kinetics of the response are similar to those for in vitro T cell responses to antigen rather than via polyclonal activation through lectin or anti-CD3 triggering, suggesting a physiological basis for the phenomenon. The stimulatory influence was blocked by the delta-selective antagonist ICI-174864, suggesting the mediation of classical opioid delta receptors. The opioid receptor specificity is further demonstrated using delta- and mu-selective agonists. The delta-selective agonists DSLET and DPDPE stimulate proliferation, whereas the mu-selective agonist DAGON was without effect.