Relationship between phosphodiesterase type 4 inhibition and anti-inflammatory activity of CI-1044 in rat airways.

The anti-inflammatory effects of CI-1044 and of the other selective PDE4 inhibitors rolipram and cilomilast were investigated in Brown-Norway (BN) rats, against lipopolysaccharide-induced tumor necrosis factor alpha (TNFalpha) production in whole blood and antigen-induced lung eosinophilia. In vitro, CI-1044 inhibited TNFalpha production with an IC(50) of 0.31 microm being equipotent to Cilomilast (IC(50) = 0.

Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory drugs.

The phosphodiesterases (PDEs) are responsible for the hydrolysis of intracellular cyclic adenosine and guanosine monophosphate (cAMP and cGMP, respectively). They are classified into 11 major families (PDE1-11) and the type 4 phosphodiesterase (PDE4) is a cAMP-specific enzyme localized in airway smooth muscle cells as well as in immune and inflammatory cells. The PDE4 activity is associated with a wide variety of diseases some of which have been related to an inflammatory state, (e.