Hypothalamic 11,12-epoxyeicosatrienoic acid attenuates fever induced by central interleukin-1β in the rat

doi:10.1016/S0304-3940(01)02115-2

Neuroscience Letters

Volume 310, Issues 2–3, 14 September 2001, Pages 141-144

https://doi.org/10.1016/S0304-3940(01)02115-2 Get rights and content

Abstract

Inhibitors of cytochrome P-450 augment fever in rats and mice, indicating that the metabolite of the enzyme is candidate of endogenous antipyretic. Cytochrome P-450 of arachidonic acid cascade leads to the formation of regioisomeric 5,6-, 8,9- 11,12- and 14,15-epoxyeicosatrienoic acid (EET). Various isomers of EET were administrated into the preoptic area and anterior hypothalamus (PO/AH) to test their influence on fever induced by interleukin-1β (IL-1β) administrated into the PO/AH in conscious rats. The IL-β-induced fever was attenuated in the 11,12-EET-pretreated rats, although 5,6-, 8,9- and 14,15-EET did not affect the fever. Intra-PO/AH injection of 11,12-EET did not alter normal body temperature. The results suggest that 11,12-EET acts in the hypothalamus as an endogenous antipyretic.

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Acknowledgements

This work was supported in part by Grant-in-Aid for Scientific Research B12557006 and Special Coordination Funds from the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government.

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Approaches targeting these harmful excessive inflammatory reactions may not only modulate the neuronal hyperexcitability induced-CPSP condition but also reduce the secondary long-term damage to brain tissues caused by acute stroke. The recognition of the anti-inflammatory effect of EETs can be traced back to as early as 1996, when CYP450 metabolites were found to be antipyretic to fever induced by central IL-1β injection in rats [110,111]. As EETs are EDHFs that induce vasodilation, the antipyresis may be due to the change in blood flow; however, this is unlikely to be the major determinant of body temperature, because no effect of EETs on non-febrile rats was found in this study, providing a clue for an anti-inflammatory role independent of their vasodilatory properties.
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Hypothalamic 11,12-epoxyeicosatrienoic acid attenuates fever induced by central interleukin-1β in the rat

Abstract

Section snippets

Acknowledgements

Brain Res.

Brain Res. Bull.

Trends Neurosci.

Cytochrome P-450 and the arachidonate cascade

FASEB J.

14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in smooth muscle cells

Am. J. Physiol.

14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E₂ production in smooth muscle cells