Phosphodiesterase 4 Inhibitors in Inflammatory Bowel Disease: A Comprehensive Review

Pooneh      Salari-Sharif; Mohammad      Abdollahi

doi:10.2174/138161210794079209

Abstract

Inflammatory bowel disease (IBD) is known as a chronic inflammation of gastrointestinal tract that its pathogenesis still is not completely understood. Several drug categories are used for management of IBD but there is no exact cure for the disease, however biological drugs targeting the inflammation of gut are on the center of attention. In investigating the anti-inflammatory drugs, phosphodiesterase inhibitors were found to be effective in different inflammatory disorders. Of them phosphodiesterase 4 (PDE4) inhibitors are considered for treatment of asthma and chronic obstructive pulmonary disease (COPD). Some of the PDE4 inhibitors showed promising efficacy in animal studies, however to date no phase III clinical study showed their effectiveness in IBD. The present study has the most relevant studies in this field. PDE4 inhibitors affect IBD in different ways including anti-inflammatory, anti-depressant, and anti-fibrotic effects. Unfortunately, the most common side effect of PDE4 inhibitors is nausea which limits its use. Tetomilast the second generation of PDE4 inhibitors showed promising effects in phase II studies with better safety profile. Other drugs in this class are ongoing phase II and III trials.

Keywords: Inflammatory bowel disease, phosphodiesterase 4 inhibitor, Crohn's disease, ulcerative colitis, Phosphodiesterase 4 Inhibitors, chronic inflammation, gastrointestinal tract, IBD, phosphodiesterase inhibitors, asthma, chronic obstructive pulmonary disease, Tetomilast, incontinence, abdominal pain, reactive oxygen metabolites, aminosalicylates, immunomodulators, Phosphodiesterase enzyme, neurodegeneration, immunomodulatory cells, NO synthesis, anti-TNF- antibody, hepatic fibrosis, growth factor-I, cyclic adenosine monophosphate, cyclic guanosine monophosphate, protein kinases, phosphorylation, rheumatoid arthritis, multiple sclerosis, endotoxin, Sildenafil, a PDE5 inhibitor, Roflumilast, rolipram, cilomilast, T-cell chemotaxis, isoenzymes