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Systems neuroscience

Heat relief

Nature Reviews Neuroscience volume 4, page 934 (2003)Cite this article

A team led by Anders Blomqvist investigated the role of microsomal prostaglandin E synthase-1 (mPges1) — which catalyses the second step in Pge2 production — in the febrile response, by knocking out its expression in mice. Mutant mice were indistinguishable from their wild-type littermates under normal physiological conditions. However, differences emerged following immune challenge with bacterial cell-wall lipopolysaccharide (LPS). Shortly after injection of LPS, the core body temperature of wild-type mice increased significantly and remained elevated for about six hours. By contrast, the temperature of immune-challenged mPges1-deficient mice did not differ from that of saline-injected controls. Direct injection of Pge2 into brains of mutants elicited a robust febrile response, confirming that these mPges1-deficient mice retained the capacity to respond to the product of mPges1 activity.

Levels of Pge2 in cerebrospinal fluid after administration of LPS mimicked the temperature pattern, increasing in wild-type subjects and remaining static in their mutant counterparts. Incubation of brain homogenates from immune-challenged mice with the substrate of mPges1, Pgh2, showed that these responses were correlated with enzymatic activity, or lack thereof, in the microsomal fraction. Reverse transcription-polymerase chain reaction was used to confirm that the physiological effects of LPS injection were due to differential expression of mPges1 in brain homogenates of wild-type and mutant mice.

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ORIGINAL RESEARCH PAPERS

  1. Engblom, D. et al. Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis. Nature Neurosci. 6, 1137–1138 (2003)

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  2. Ivanov, A. I. et al. Platelet-activating factor: a previously unrecognized mediator of fever. J. Physiol. (Lond.) 17 October 2003 (doi: 10.1113/jphysiol.2003.055616)

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Authors
  1. Suzanne Farley
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Farley, S. Heat relief. Nat Rev Neurosci 4, 934 (2003). https://doi.org/10.1038/nrn1292

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  • DOI: https://doi.org/10.1038/nrn1292

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