Deletion of Prostaglandin E 2 Synthesizing Enzymes in Brain Endothelial Cells Attenuates Inflammatory Fever

• Published in: The Journal of neuroscience 2014-08, Vol.34 (35), p.11684-11690
• Main Authors: Wilhelms, Daniel Björk, Kirilov, Milen, Mirrasekhian, Elahe, Eskilsson, Anna, Kugelberg, Unn Örtegren, Klar, Christine, Ridder, Dirk A., Herschman, Harvey R., Schwaninger, Markus, Blomqvist, Anders, Engblom, David
• Format: Article
• Language: English
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.1838-14.2014

Fever is a hallmark of inflammatory and infectious diseases. The febrile response is triggered by prostaglandin E 2 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 PGE 2 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 PGE 2 synthesis in brain endothelial cells is critical for inflammation-induced fever.