15-keto Prostaglandin E2 (15-keto PGE2) is a metabolite of PGE2 formed by 15-hydroxy prostaglandin dehydrogenase (15-PGDH).¹ Unlike PGE2, 15-keto PGE2 does not bind effectively to the PGE2 receptors EP2 and EP4 expressed in CHO cells (Kis = 2.6 and 15 µM, respectively) or induce adenylate cyclase activity in the same cells (EC50s = 1.8 and >33 µM, respectively). However, it does bind to EP2 and EP4 in HEK cells expressing these receptors (IC50s = 0.117 and 2.82 µM, respectively), as well as induces cAMP formation (EC50s = 0.137 and 0.426 µM, respectively) and the transcriptional activity of β-catenin/TCF in the same cells.² 15-keto PGE2 inhibits CD3-CD28-MHC-I-induced proliferation of isolated human CD4+ T cells in a concentration-dependent manner.³ It also reduces mortality in a mouse model of LPS-induced sepsis when administered at a dose of 15 mg/kg.⁴