Inhibition of Cyclo-oxygenase Attenuates the Metabolic Response to Endotoxin in Humans

Revhaug, Arthur; Michie, Hamish R.; Manson, James; Watters, James M.; Dinarello, Charles A.; Wolff, Sheldon M.; Wilmore, Douglas W.

doi:10.1001/archsurg.1988.01400260042004

Cited by 163 publications

(36 citation statements)

References 21 publications

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“…However, their exact role remains obscure. In different in vivo studies prostanoids have been shown to enhance, 11,12 to be without significance, 13,14 or to attenuate 15 the acute phase response. In light of in vitro experiments the attenuation of the acute phase response seems to be most likely, because prostaglandin E 2 (PGE 2 ) that is released from Kupffer cells in response to proinflammatory signals can inhibit the synthesis of IL-6 16 and tumor necrosis factor ␣ 17 in an autocrine feedback inhibition loop.…”

mentioning

confidence: 99%

Induction by interleukin 6 of Gs-coupled prostaglandin E2 receptors in rat hepatocytes mediating a prostaglandin E2-dependent inhibition of the hepatocyte’s acute phase response

2000

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confidence: 99%

Induction by interleukin 6 of Gs-coupled prostaglandin E2 receptors in rat hepatocytes mediating a prostaglandin E2-dependent inhibition of the hepatocyte’s acute phase response

2000

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“…However, there is substantial evidence against direct involvement of prostanoids in the actions of cytokines on liver metabolism (Sobrado et al 1983;Johnston, 1985;Revhaug et al 1988;Evans er al. 1989).…”

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confidence: 99%

Dietary manipulation of the inflammatory response

Grimble

1992

Proc. Nutr. Soc.

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“…In anesthetized rats with LPS-induced endotoxemia, indomethacin did not change the fall in MAP, but it prevented the increase in RSNA (30) and, in human volunteers administered E. coli endotoxin, treatment with ibuprofen attenuated the increases in heart rate and plasma catecholamines (25). The effects of COX inhibitors on the resting levels or baroreflex control of CSNA have not, however, been investigated.…”

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confidence: 99%

“…Both intracarotid and central administration of prostaglandin E 2 (PGE 2 ) have been shown to produce similar changes to those seen during sepsis: fever, tachycardia, and an increase in RSNA (3,4). Furthermore, inhibitors of the cyclooxygenase (COX) pathway, which inhibit prostaglandin production, prevent the tachycardia and the release of catecholamines and stress hormones in response to endotoxin in humans (25), as well as the increase in RSNA in response to LPS in anesthetized rats (30). In addition, the late increase in RSNA following transient, mild exposure to LPS in rabbits was reduced following acetylsalicylate administration (26).…”

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confidence: 99%

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis

Booth

Ramchandra

Calzavacca

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Booth LC, Ramchandra R, Calzavacca P, May CN. Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis. Am J Physiol Regul Integr Comp Physiol 307: R75-R81, 2014. First published April 30, 2014 doi:10.1152/ajpregu.00450.2013.-Effective treatment of sepsis remains a significant challenge in intensive care units. During sepsis, there is widespread activation of the sympathetic nervous system, which is thought to have both beneficial and detrimental effects. The sympathoexcitation is thought to be partly due to the developing hypotension, but may also be a response to the inflammatory mediators released. Thus, we investigated whether intracarotid infusion of prostaglandin E2 (PGE2) induced similar cardiovascular changes to those caused by intravenous infusion of Escherichia coli in sheep and whether inhibition of prostaglandin synthesis, with the nonselective cyclooxygenase inhibitor indomethacin, administered at 2 and 8 h after the onset of sepsis, reduced sympathetic nerve activity (SNA), and heart rate (HR). Studies were performed in conscious sheep instrumented to measure mean arterial pressure (MAP), HR, cardiac SNA (CSNA), and renal SNA (RSNA). Intracarotid infusion of PGE2 (50 ng·kg Ϫ1 ·min Ϫ1 ) increased temperature, CSNA, and HR, but not MAP or RSNA. Sepsis, induced by infusion of E. coli, increased CSNA, but caused an initial, transient inhibition of RSNA. At 2 h of sepsis, indomethacin (1.25 mg/kg bolus) increased MAP and caused reflex decreases in HR and CSNA. After 8 h of sepsis, indomethacin did not alter MAP, but reduced CSNA and HR, without altering baroreflex control. These findings indicate an important role for prostaglandins in mediating the increase in CSNA and HR during the development of hyperdynamic sepsis, whereas prostaglandins do not have a major role in determining the early changes in RSNA.sepsis; cardiac sympathetic nerve activity; renal sympathetic nerve activity; PGE2; indomethacin; baroreflex curve; sheep SEPSIS AND SEPTIC SHOCK ARE the chief causes of death in intensive care units with mortality rates of between 30 and 70% when combined with multiorgan failure (2, 20, 21, 28). Although the incidence of sepsis is increasing, our knowledge of the pathology is limited, and current treatments, including volume resuscitation and vasoconstrictors, are only marginally effective. In human septic patients the most common hemodynamic profile is a hyperdynamic circulation, characterized by peripheral vasodilatation and hypotension accompanied by an increased cardiac output (16,17). These changes are accompanied by activation of the sympathetic nervous system, as demonstrated by increased circulating levels of plasma catecholamines in septic humans (12), increased renal sympathetic nerve activity (RSNA) in endotoxemic rats (22,30), and increased SNA to the heart and kidneys in sheep with hyperdynamic sepsis (24). It would be expected that an increase in SNA would be beneficial in sepsis, for example, by maintaining arterial pressure; however there...

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Inhibition of Cyclo-oxygenase Attenuates the Metabolic Response to Endotoxin in Humans

Cited by 163 publications

References 21 publications

Induction by interleukin 6 of Gs-coupled prostaglandin E2 receptors in rat hepatocytes mediating a prostaglandin E2-dependent inhibition of the hepatocyte’s acute phase response

Induction by interleukin 6 of Gs-coupled prostaglandin E2 receptors in rat hepatocytes mediating a prostaglandin E2-dependent inhibition of the hepatocyte’s acute phase response

Dietary manipulation of the inflammatory response

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis

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