adenylyl cyclase-cAMP-PKA downregulation alteration

Elevated cAMP has adverse effect on the immune system as one case. It desensitize the innate and in some cases the adaptive immune T and B cells.

Does anyone know of any drugs/methods etc.. to up-regulate cAMP levels in a uniform manner safely? The Phosphodiesterases (PDEs) in general do this by degrading cAMP but they specific PDEs to specific cAMP control PDE-1, PDE-2 .... Caffeine and other methlxanthines such as theophyline are general PDE(x) but don't get great  intercellular as they don't cross the cell wall easily. The dosages needed would be unsafe to use in some cases.

Other methods would be to  block the control ligand on the cell surface, also risky.

Are there any approaches besides the use of a specific PDE(1,2,3,4,5...) to degrade cAMP and lower its level?