Full name: Phosphodiesterase 4

Size: 50–125 kDa¹

Family: PDE4 isoenzyme subfamily (PDE4A to PDE4D) of the phosphodiesterase enzyme family²

Major cellular sources: Neutrophils, T cells, macrophages, monocytes, eosinophils, DCs, NK cells, epithelial cells, keratinocytes, chondrocytes, and synoviocytes^2,3

Major cellular targets: Epithelial cells, such as those lining the airways³

Disease states associated with: Asthma, chronic obstructive pulmonary disease, psoriasis, psoriatic arthritis, and Behçet’s disease^2,4

Major physiologic functions:

• Each enzyme within the PDE4 family specifically targets cAMP for degradation and selectively hydrolyses cAMP into AMP, downstream controlling a network of pro-inflammatory and anti-inflammatory mediators.^2,3
• PDE4 inhibition targets a central pathogenic process that bypasses complex antigen receptor–specific immunoregulatory mechanisms. Thus, selective PDE4 inhibition has been investigated for numerous autoimmune conditions, including ankylosing spondylitis, Alzheimer’s disease, psoriasis, psoriatic arthritis, sarcoidosis, systemic lupus erythematosus, inflammatory bowel disease, atopic dermatitis, rheumatoid arthritis, and multiple sclerosis.²

AMP: adenosine monophosphate; cAMP: cyclic AMP; DC: dendritic cell; IFN-γ: interferon gamma; IL: interleukin; NK: natural killer; TNF: tumor necrosis factor.