Molecular and cellular actions of Pentoxifylline
Pentoxifylline is a xanthine derivative drug with a wide range of
actions at the cellular and molecular level. pentoxifylline has
rheological actions increasing erythrocyte deformability and was
originally licensed for the treatment of peripheral vascular disease on
the basis of suggested improvement of microvascular and capillary blood
flow [7]. More recently pentoxifylline has been determined to have
extensive anti-inflammatory properties [8]. pentoxifylline inhibits
5’-nucleotidase and phosphodiesterases (PDE). PDE inhibition results in
increased cAMP levels, increased protein kinase A (PKA) activity and
altered transcriptional regulation of pro-inflammatory genes through
modulation of the NFκB/IκB pathway [8]. Pentoxifylline downregulates
transcription and expression levels of TNFα, IL1b, IL6, IFNγ, ICAM1 and
VCAM1. pentoxifylline 5’-nucleotidase inhibition reduces the production
of adenosine and inosine from adenosine monophosphate (AMP) and inosine
monophosphate (IMP) respectively. Pentofxyfilline appears able to
downregulate the pathologically important pro-inflammatory adenosine
receptor A2A pathway [9]. These effects contribute to the extensive
actions of pentoxifylline in reducing pro-inflammatory signals. For
example, pentoxifylline reduces cytokine release from pulmonary
macrophages derived from patients with sarcoidosis [10]. Lungs have
the highest proportion of total resident macrophages in the human body,
around 1 trillion.