Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation

Intracellular levels of cyclic nucleotide second messengers are regulated p redominantly by the complex superfamily of cyclic nucleotide phosphodiester ase (PDE) enzymes. Recent advances in our understanding of the molecular ph armacology of these enzymes has led to their identification as biologic reg ulators of certain disease: states and the development of isozyme-selective inhibitors as potential therapeutic agents. A large body of in vitro and p reclinical data suggests the therapeutic utility of PDE4 inhibitors as pote nt antiinflammatory agents. Early clinical trials with selective PDE inhibi tors substantiate this approach while highlighting pharmacodynamic and toxi cologic pitfalls inherent to the inhibition of specific PDE isozymes, This commentary will review our current understanding of PDE inhibitors as immun omodulatory agents. (C) 1999 Elsevier Science Inc.