Peroxisome proliferator-activated receptor γ agonists -: Potential use for treating chronic inflammatory diseases

The success of PPARγ agonists in the treatment of inflammatory, neoplastic, and atherosclerotic diseases depends on multiple factors, including the expression of PPARγ in target tissues, the activity of PPARγ in modulating the disease of interest, and the ability of ligands to activate PPARγ in vivo without inducing toxicity. Recognition of the potential human clinical applications of PPARγ agonists has led to a recent explosion of research and publications regarding this molecule. Several pharmaceutical companies are developing newer and more potent TZDs as well as other non-TZD PPARγ agonists. We will undoubtedly see numerous clinical trials of these agents in human inflammatory and neoplastic diseases in the near future. Whether PPARγ agonists will have significant efficacy alone, serve as adjuncts for other therapeutic agents, or prove to have minimal efficacy in human diseases remains to be determined. If large doses of TZDs are required for activity, toxicity will also be a concern. The significant in vitro antiinflammatory and antineoplastic activity and the success thus far of in vivo animal models of inflammatory disease suggest that manipulation of PPARγ, either pharmacologically or perhaps by gene therapy, will likely be useful in a number of human diseases.