Differential sensitivity in the sites of fever production by prostaglandin E1 within the hypothalamus of the rat.

Stitt, John T.

doi:10.1113/jphysiol.1991.sp018378

Cited by 81 publications

(50 citation statements)

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“…PGE 2 acts locally in the preoptic/anterior area of the hypothalamus (44,47,52) where PGE receptor subtypes are expressed: namely EP1-R, EP3-R, and EP4-R (37) that have been implicated in fever. Agonist/antagonist studies concluded that PGE 2 acts mainly, if not solely, through the EP1-R subtype to mediate fever (33).…”

Section: Discussionmentioning

confidence: 99%

“…8) to induce expression of cyclooxygenase-2 (COX-2) (6,22). The activity of this enzyme results in the cyclooxygenation of arachidonic acid and subsequently the production of PGE 2 , which acts largely in the anterior hypothalamus/preoptic area (47). COX-2 is present in basal conditions in the brain (3,41), but in inflammation, it is induced specifically in the endothelium of brain capillaries (18,25).…”

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confidence: 99%

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Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

Mouihate¹,

Ms²,

Nakamura

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus. Am J Physiol Regul Integr Comp Physiol 283: R800-R805, 2002; 10.1152/ ajpregu.00258.2002The fever response is blunted at near term. As the enzyme cyclooxygenase-2 (COX-2) plays a critical role in fever development, we measured its expression in rat hypothalamus during pregnancy and lactation. Western blot analysis revealed a 72-kDa COX-2-immunoreactive band in non-immune-challenged, pregnant rats at day 15 of pregnancy. In contrast, it was almost undetectable at near term and at lactation day 5. COX-2 was significantly induced at the 15th day of pregnancy and at the 5th lactating day after intraperitoneal lipopolysaccharide (50 g/kg). However, this COX-2 induction was significantly reduced at near term compared with values before and after term. The protein levels of the EP3 receptor in the hypothalamus, one of the prostaglandin E 2 (PGE2) receptors suggested to be a key receptor for fever induction, were unaffected throughout the pregnancy and lactation in both non-immune-challenged and lipopolysaccharide-treated rats. These data suggest that suppression of fever at near term is associated with a significantly reduced induction of COX-2 by lipopolysaccharide, resulting in a reduced production of PGE 2. Altered expression of the EP3 receptor does not seem to be involved in this fever refractoriness at near term.cyclooxygenase-2; parturition; lipopolysaccharide; prostaglandin receptor; EP3 receptor FEVER, A MAJOR PART of host defense, is thought to be of beneficial and adaptive value (15). Thus the inability to develop a fever response to pathogens can be detrimental (16). An absent or reduced fever has been observed in pregnant animals at near term (14) and, in some circumstances, is associated with abortion or mortality (23). This febrile refractoriness has been observed in many species, including guinea pig (55), rabbits (28), sheep (14), and rats (7,23,24), and has been observed in response to both peripherally injected pyrogens (14, 23, 55) and, to a lesser extent, to centrally infused prostaglandins (7,24,48). The fact that fever suppression is most dramatic in response to systemically administered LPS suggests that several steps in the cascade of responses to peripherally injected LPS may be affected.In response to bacterial pyrogens such as LPS, immunocompetent cells generate endogenous cytokines, which signal to the central nervous system through either humoral or neuronal pathways (for review, see Ref. 8) to induce expression of cyclooxygenase-2 (COX-2) (6, 22). The activity of this enzyme results in the cyclooxygenation of arachidonic acid and subsequently the production of PGE 2 , which acts largely in the anterior hypothalamus/preoptic area (47). COX-2 is present in basal conditions in the brain (3, 41), but in inflammation, it is induced specifically in the endothelium of brain capillaries (18,25). Levels of COX-2 have been correlated to levels of PGE 2 during LPS-induced fever (54). Because...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

Mouihate¹,

Ms²,

Nakamura

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…There are a number of lines of evidence suggesting that PGs are essential in mediating febnile response (Stitt, 1986(Stitt, , 1991Saper and Breder, 1992) and that this physiological event involves the PVN, because lesion of this hypothalamic nucleus reduces the LPSinduced fever, but not following intracerebroventricubar injection of high doses of PGE2 (Hornet al, 1994). Therefore, pathways independent or unrelated to the PVN should be considered in the generation of fever by this particular PG.…”

Section: Cox-1 Isoformmentioning

confidence: 99%

Effect of Acute Systemic Inflammatory Response and Cytokines on the Transcription of the Genes Encoding Cyclooxygenase Enzymes (COX‐1 and COX‐2) in the Rat Brain

Lacroix

Rivest

1998

Journal of Neurochemistry

251

136

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Abstract:The aim of this study was to investigate the influence of the acute-phase response and the promflammatory cytokines on the transcription of the genes encoding the limiting enzymes for the production of prostaglandins, cyclooxygenase (COX)-1 and COX-2, in the rat brain. The bacterial endotoxin lipopolysaccharide (intravenous and intraperitoneal) and turpentine (intramuscular) were used as different models of inflammation in adult male rats. Animals were also killed at various times after intravenous administration of interleukin-1/3, tumor necrosis factor-a, and interleukin-6, and mRNAs encoding COX-1 and COX-2 were assayed by in situ hybridization histochemistry. A profound transcriptional activation of the gene encoding COX-2 was detected over blood vessels of the entire brain microvasculature, choroid plexus, and leptomeninges of lipopolysaccharide-challenged rats. Injection of the endotoxin intravenously also increased COX-2 gene expression within parvocellular division of the hypothalamic paraventricular nucleus. It is interesting that intramuscular turpentine injection stimulated transcription of COX-2 along endothelium of brain capillaries, and the signal of this transcript paralleled the inflammation of the left hind limb. A robust COX-2 mRNA signal was detected rapidly in the brain microvessels of interleukin-1~3-injectedrats, whereas tumor necrosis factor-a administration caused a modest but significant induction of this transcript. In contrast, intravenous injection of interleukin-6 did not alter genetic expression of COX-2, and none of the above described models affected the synthesis of COX-1 gene in the rat brain. These results indicate that specific cell populations, in particular vascular-and/or perivascular-associated cells, are responsible for the central production of prostaglandins during systemic inflammation, and circulating interleukin-1~is likely to be a potent mediator of this response. Key Words: In situ hybridization histochemistry-Immune responseInterleukin -1 -Interleukin -6-Leptomeninges -Lipopolysaccharide-Microvessels--Paraventricular nucleus of the hypothalamus-Prostaglandins-Tumor necrosis factor-Turpentine insult.

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“…IL-1 type 1 receptor mRNA is coexpressed in the cyclooxygenase-2 mRNA positive cells in the blood vessels of the organum vasculosum laminae terminalis (OVLT) [24]. The OVLT has a very high density of prostaglandin binding sites [25], and the region is highly sensitive to prostaglandin in increasing body temperature [26]. These results suggest that the endogenous IL-1 increases body temperature through the OVLT.…”

Section: Discussionmentioning

confidence: 69%

Interleukin-1.BETA. Administered Intracerebroventricularly Stimulates the Release of Noradrenaline in the Hypothalamic Paraventricular Nucleus via Prostaglandin in the Rat.

Tsumori¹,

Shibasaki

Hotta³

et al. 1998

Endocr J

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Abstract. We evaluated the effect of intracerebroventricular (icy) administration of interleukin (IL) -1fl on the rectal temperature and the release of noradrenaline (NA) in the hypothalamic paraventricular nucleus (PVN) of the rat. IL-1fl increased rectal temperature at doses ranging from 300 pg to 300 ng, whereas it, at doses ranging from 3 ng to 300 ng, significantly stimulated the release of NA in the PVN measured by intracerebral microdialysis.The stimulatory effect of IL-1~ on the release of NA was blocked by the subcutaneous injection of indomethacin. These findings suggest that IL-1fl stimulates the release of NA in the PVN via prostaglandin, and that the release of NA in the PVN is not necessarily related to the increase in body temperature.

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Differential sensitivity in the sites of fever production by prostaglandin E1 within the hypothalamus of the rat.

Cited by 81 publications

References 19 publications

Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus

Effect of Acute Systemic Inflammatory Response and Cytokines on the Transcription of the Genes Encoding Cyclooxygenase Enzymes (COX‐1 and COX‐2) in the Rat Brain

Interleukin-1.BETA. Administered Intracerebroventricularly Stimulates the Release of Noradrenaline in the Hypothalamic Paraventricular Nucleus via Prostaglandin in the Rat.

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