Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest. Here we elucidated the structures of four new host-protective molecules produced in neutrophil-endothelial co-cultures, and present in human and mouse tissues after sterile inflammation or infection. These bioactive molecules contained conjugated triene and diene double bonds with each carrying a 13-carbon position alcohol and were derived from n-3 docosapentaenoic acid (DPA, C22:5). These compounds, termed 13-series resolvins (RvT), demonstrated potent protective actions increasing mice survival during Escherichia coli infections. RvT also regulated human and mouse phagocyte responses stimulating bacterial phagocytosis and regulating inflammasome components. Their biosynthesis during neutrophil-endothelial cell interactions was initiated by endothelial cyclooxygenase-2 (COX-2) and increased by atorvastatin via S-nitrosylation of COX-2. The actions of atorvastatin and RvT were additive in E. coli infections in mice where they accelerated resolution of inflammation and increased survival >；60%.
