Peroxisome proliferator-activated receptor (PPAR) gamma: a new target for the treatment of inflammatory bowel disease

The peroxisome proliferator-activated receptor (PPAR) gamma is highly expre ssed in the colon mucosa. In vitro, it regulates inflammation. Aim - To evaluate the anti-inflammatory functions of PPAR gamma agonist dur ing a trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Methods - Colitis was induced in Balb/c mice after intra-rectal administrat ion of TNBS. The intensity of inflammation was assessed 2 and 5 days after colitis induction by macroscopic and histologic scores and by the quantific ation of colon myeloperoxidase (MPO), IL-1 beta and TNF alpha mRNA concentr ations. The therapeutic role of PPAR gamma agonist given by oral gavage was assessed in preventive and treatment modes. Results - TNBS induced severe macroscopic and histologic lesions, with high mucosal MPO, IL-1 beta and TNF alpha mRNA concentrations. PPAR gamma agoni st given preventively or in treatment mode allowed a significant decrease o f macroscopic and histologic scores through a normalization of MPO, IL-1 be ta and TNF alpha mRNA concentrations. Conclusion - PPAR gamma agonist decreases the intensity of TNBS induced col itis through normalization of IL-1 beta and TNF alpha expression. PPAR gamm a agonists may be proposed as new therapeutic agents in inflammatory bowel diseases.