Abstract
Cyclic nucleotide second messengers (cAMP and cGMP) play a central role in signal transduction and regulation of physiologic responses. Their intracellular levels are controlled by the complex superfamily of cyclic nucleotide phosphodiesterase (PDE) enzymes. Continuing advances in our understanding of the molecular pharmacology of these enzymes has led to the development of selective inhibitors as therapeutic agents for disease states ranging from cancer and heart failure to depression and sexual dysfunction. Several PDE types have been identified as therapeutic targets for immune/inflammatory diseases. This article briefly reviews the available in vitro, preclinical, and clinical data supporting the potential for selective PDE inhibitors as immunomodulatory agents.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Adjuvants, Immunologic / therapeutic use
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Antigen-Presenting Cells / drug effects
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Antigen-Presenting Cells / enzymology
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Clinical Trials as Topic
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Cyclic AMP / physiology
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Cyclic GMP / physiology
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Endothelium / drug effects
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Endothelium / enzymology
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Granulocytes / drug effects
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Granulocytes / enzymology
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Humans
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Lymphocytes / drug effects
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Lymphocytes / enzymology
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Mast Cells / drug effects
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Mast Cells / enzymology
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Models, Biological
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Phosphodiesterase Inhibitors / pharmacology*
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Phosphodiesterase Inhibitors / therapeutic use
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Phosphoric Diester Hydrolases / chemistry
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Phosphoric Diester Hydrolases / classification
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Phosphoric Diester Hydrolases / physiology*
Substances
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Adjuvants, Immunologic
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Phosphodiesterase Inhibitors
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Cyclic AMP
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Phosphoric Diester Hydrolases
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Cyclic GMP