Enhanced Effects of Prostaglandin E<sub>1</sub> and Dibutyryl Cyclic AMP upon Human Lymphocytes in the Presence of Cortisol

John Mendelsohn; Michael M. Multer; Robert F. Boone

doi:10.1172/JCI107397

Enhanced Effects of Prostaglandin E₁ and Dibutyryl Cyclic AMP upon Human Lymphocytes in the Presence of Cortisol

John Mendelsohn, Michael M. Multer, and Robert F. Boone

Published September 1, 1973 - More info

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Abstract

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 h 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.