TY - JOUR T1 - Deletion of Prostaglandin E<sub>2</sub> Synthesizing Enzymes in Brain Endothelial Cells Attenuates Inflammatory Fever JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11684 LP - 11690 DO - 10.1523/JNEUROSCI.1838-14.2014 VL - 34 IS - 35 AU - Daniel Björk Wilhelms AU - Milen Kirilov AU - Elahe Mirrasekhian AU - Anna Eskilsson AU - Unn Örtegren Kugelberg AU - Christine Klar AU - Dirk A. Ridder AU - Harvey R. Herschman AU - Markus Schwaninger AU - Anders Blomqvist AU - David Engblom Y1 - 2014/08/27 UR - http://www.jneurosci.org/content/34/35/11684.abstract N2 - 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. ER -