RT Journal Article SR Electronic T1 Deletion of Prostaglandin E2 Synthesizing Enzymes in Brain Endothelial Cells Attenuates Inflammatory Fever JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 11684 OP 11690 DO 10.1523/JNEUROSCI.1838-14.2014 VO 34 IS 35 A1 Daniel Björk Wilhelms A1 Milen Kirilov A1 Elahe Mirrasekhian A1 Anna Eskilsson A1 Unn Örtegren Kugelberg A1 Christine Klar A1 Dirk A. Ridder A1 Harvey R. Herschman A1 Markus Schwaninger A1 Anders Blomqvist A1 David Engblom YR 2014 UL http://www.jneurosci.org/content/34/35/11684.abstract AB Fever is a hallmark of inflammatory and infectious diseases. The febrile response is triggered by prostaglandin E2 synthesis mediated by induced expression of the enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES-1). The cellular source for pyrogenic PGE2 remains a subject of debate; several hypotheses have been forwarded, including immune cells in the periphery and in the brain, as well as the brain endothelium. Here we generated mice with selective deletion of COX-2 and mPGES1 in brain endothelial cells. These mice displayed strongly attenuated febrile responses to peripheral immune challenge. In contrast, inflammation-induced hypoactivity was unaffected, demonstrating the physiological selectivity of the response to the targeted gene deletions. These findings demonstrate that PGE2 synthesis in brain endothelial cells is critical for inflammation-induced fever.