Factors influencing the immunomodulating effect of met-enkephalin: Role of mitogen dose, stage of cell activation, and time of opioid administration

Abstract

Met-enkephalin in a concentration range of 10⁻¹⁵ to 10⁻⁹ M exhibited an immunomodulating effect upon concanavalin A-induced proliferation of mouse lymphocytesin vitro. The effect of met-enkephalin was shown to depend on the stage of lymphocyte activation, the time of opioid administration, and the dose of mitogen. Met-enkephalin produced the maximal effect when given in the phases of increase or decrease of the proliferative response. Met-enkephalin augmented the proliferative response to the suboptimal dose of concanavalin A and, on the contrary, inhibited the response to the optimal dose of mitogen. Administration of met-enkephalin at different times could both inhibit and stimulate proliferation depending on the stage of lymphocyte activation. An inhibitory effect was induced by δ-class opioid ligand, while κ-ligand was responsible for stimulation. Naloxone abolished the stimulating effect of opioids.