THE ROLE OF PDE4 IN THE INFLAMMATORY CELL1*

PDE4 IS THE DOMINANT PDE IN INFLAMMATORY CELLS AND FUNCTIONS TO TERMINATE THE ACTION OF cAMP, AN INTRACELLULAR SECONDARY MESSENGER

immune-cell.svg

cAMP maintains immune homeostasis

  • PDE4 inhibition elevates intracellular cAMP levels

Increased cAMP downregulates the inflammatory response

  • cAMP suppresses release of pro-inflammatory mediators
  • cAMP promotes the release of anti-inflammatory mediators

These pro- and anti-inflammatory mediators have been implicated in psoriatic arthritis and psoriasis.

OTEZLA, A SELECTIVE SMALL-MOLECULE INHIBITOR OF PDE4, DEMONSTRATED PHARMACOLOGY IN CELLULAR MODELS1*

  • OTEZLA inhibits production of TNF-α in human peripheral blood mononuclear cells, synovial cells, plasmacytoid dendritic cells, epidermal keratinocytes, lamina propria mononuclear cells, and whole blood
  • Other effects include the inhibition of IFN-γ and IL-23A (IL-23p19) production and the elevation of IL-10 production by mononuclear cells, inhibition of GM-CSF, IFN-γ, TNF-α, IL-5, IL-13, and IL-17 by T cells, and the inhibition of IL-8 production by polymorphonuclear cells
  • OTEZLA also inhibited the formation of osteoclasts, cells that can cause bone resorption

* Clinical significance has not been established.

cAMP, cyclic adenosine monophosphate; IL, interleukin; PDE4, phosphodiesterase 4; TNF, tumour necrosis factor.