The present invention relates to compositions and methods for preventing and reducing inflammation and preventing and treating diseases and disorders associated with inflammation. It has been shown that CRADD plays a pivotal role in maintaining the integrity of endothelial monolayers. The recombinant cell-penetrating CRADD protein (CP-CRADD)-based compositions and methods described herein provide for the development of a novel treatment for inflammatory vascular disorders including cardiovascular, cerebrovascular, respiratory, gastrointestinal, and renal systems.