Calcium Ionophore A 23 187 in the Presence of Phorbol Ester PMA: A Potent Inducer of Interleukin 2 and Interferon-γ Synthesis by Human Blood Cells

Abstract

Cultures of human blood mononuclear cells incubated with the calcium ionophore A 23 187 in the presence of the tumor promoter phorbol 12-myristate-13-acetate (PMA) produced 5-10 times more of the lymphokines interleukin 2 (IL 2) and interferon-gamma (IFN-γ) than cultures which were stimulated with other combinations of inducing agents and PMA. Especially at low protein concentrations, the amount of ionophore which is necessary to induce maximal quantities of both lymphokines was determined by the protein content of the culture medium. The synthesis of the two lymphokines was inhibited by low doses of Mn ++ which competes with Ca ++ for binding to the ionophore. This suggests the importance of Ca ++ in the induction process. The synthesis rates of IL 2 were maximal 10–12 h, and those of IFN-γ 20–40 h after induction. Maximal titers of IL 2 were detected 48 h after the addition of A 23187 and PMA to the cultures, and the highest IFN-γ levels 12–24 h later.