Abstract
We studied the febrile response in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal isomerase expressed in cytokine-sensitive brain endothelial cells. These animals showed no fever and no central prostaglandin (PG) E2 synthesis after peripheral injection of bacterial-wall lipopolysaccharide, but their pyretic capacity in response to centrally administered PGE2 was intact. Our findings identify mPGES-1 as the central switch during immune-induced pyresis and as a target for the treatment of fever and other PGE2-dependent acute phase reactions elicited by the brain.
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Acknowledgements
Supported by the Swedish Research Council (07879, 14706 and 12573) and Cancer Foundation (4095). We thank B. Koller for the gift of EP3–deficient mice.
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Engblom, D., Saha, S., Engström, L. et al. Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis. Nat Neurosci 6, 1137–1138 (2003). https://doi.org/10.1038/nn1137
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DOI: https://doi.org/10.1038/nn1137
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