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Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis

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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Figure 1: Febrile response following peripheral immune challenge.
Figure 2: PGE2 levels and synthesis after immune challenge in Ptges+/+ and Ptges−/− mice 3 h after i.p. injection of LPS or saline.
Figure 3: PGE2-induced febrile response.

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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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Correspondence to Anders Blomqvist.

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The authors declare no competing financial interests.

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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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