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Microsomal prostaglandin E synthase-1 is the central switch during immune-induced pyresis
David Engblom1, Sipra Saha, Linda Engström
1Division of Cell Biology, Faculty of Health Sciences, University of Linköping, S-581 85 Linköping, Sweden.
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.
Insights
Mice lacking microsomal prostaglandin E synthase-1 (mPGES-1) did not develop fever after lipopolysaccharide injection, indicating mPGES-1 is crucial for immune-induced fever. This enzyme is a potential therapeutic target for fever treatment.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Fever is a key component of the acute phase response.
- Prostaglandin E2 (PGE2) is a critical mediator of fever.
- The role of microsomal prostaglandin E synthase-1 (mPGES-1) in central fever induction is not fully understood.
Purpose of the Study:
- To investigate the role of mPGES-1 in the febrile response to peripheral immune challenge.
- To determine if mPGES-1 is essential for central PGE2 synthesis during fever.
Main Methods:
- Utilized mPGES-1 deficient mice.
- Administered bacterial-wall lipopolysaccharide peripherally.
- Measured fever response and central PGE2 synthesis.
- Assessed pyretic capacity following central PGE2 administration.
Main Results:
- Mice deficient in mPGES-1 exhibited no fever and no central PGE2 synthesis after peripheral lipopolysaccharide injection.
- The pyretic response to centrally administered PGE2 remained intact in mPGES-1 deficient mice.
- These findings pinpoint mPGES-1 as the central mediator of immune-induced fever.
Conclusions:
- Microsomal prostaglandin E synthase-1 (mPGES-1) is essential for fever development in response to peripheral immune stimuli.
- mPGES-1 acts as a critical switch for central prostaglandin E2 synthesis during pyresis.
- Targeting mPGES-1 offers a potential therapeutic strategy for managing fever and related inflammatory conditions.
