Control of mitogen-induced lymphocyte activation: I. The effect of cyclic AMP on DNA and RNA synthesis in PHA-stimulated cells

The role of cyclic AMP in immune responses remains controversial. Although cyclic AMP and compounds which elevate cyclic AMP levels have been shown to enhance immune responses, several recent reports have shown that the addition of cyclic AMP will depress PHA-induced blastogenesis. The data reported here involve the use of much wider dose ranges of PHA and cyclic AMP than reported heretofore. When supraoptimal doses of PHA are used, the addition of cyclic AMP, or drugs which raise intracellular cyclic AMP levels, results in an enhancement of DNA and RNA synthesis; this effect we have termed cyclic AMP-mediated high dose recovery. Measurements of intracellular cyclic AMP levels following exposure to PHA-MR69 and/or cyclic AMP reveal that elevated cyclic AMP levels occur throughout the cell culture period. This demonstrates that elevated cyclic AMP levels may alter macromolecular synthetic patterns at points in time well after the initial activating event.