Enhanced effects of prostaglandin E₁ and dibutyryl cyclic AMP upon human lymphocytes in the presence of cortisol

The combined effects of cortisol and agents acting through a cyclic AMP mediated mechanism have been studied in cultures of highly purified human peripheral lymphocytes. Incubation with prostaglandin E1 (PGE1), dibutyryl cyclic AMP, or cortisol results in a concentration dependent inhibition of [³H]thymidine incorporation by both unstimulated and phytohemagglutinin (PHA) stimulated lymphocytes, and PHA induced morphologic transformation is prevented. When cortisol and PGE1 (or dibutyryl cyclic AMP) are added together to lymphocyte cultures, enhanced inhibitory effects are observed. Incubation of unstimulated or PHA stimulated lymphocytes with PGE1 results in an elevation of intracellular cyclic AMP levels within 20 min. The concentration of cyclic AMP gradually returns to base line levels over a 1-6 hr period of time. Cortisol alone does not significantly alter cyclic AMP concentrations. However, incubation with PGE1 in the presence of cortisol results in a greater stimulation of intracellular cyclic AMP levels than that observed with PGE1 alone. These findings suggest that cortisol may act synergistically with PGE1 to elevate lymphocyte cyclic AMP levels and to regulate [³H]thymidine incorporation and transformation.