Immune-to-brain signaling and central prostaglandin E<sub>2</sub>synthesis in fasted rats with altered lipopolysaccharide-induced fever

Inoue, Wataru; Somay, Gokce; Poole, Stephen; Luheshi, Giamal N.

doi:10.1152/ajpregu.90335.2008

Cited by 40 publications

(49 citation statements)

References 58 publications

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“…The presence of an increased drive to eat in CR animals was supported by previous research, where fooddeprived, IL-1-treated rats ate ϳ60% more food than ad libitum-fed animals also administered with IL-1 and ϳ40% more than ad libitum-fed rats not administered with IL-1 (57). Further investigations involving food deprivation have demonstrated that LPS-induced reductions in food intake and weight loss are attenuated (24) as are LPS-induced increases in T b and some cytokine levels (34). The drive to eat in these fooddeprived animals, and also in the CR animals in the present study, may be more pronounced than actually displaying sickness behavior.…”

Section: Cr and Sickness Behaviormentioning

confidence: 43%

“…Curiously, the CR50% animals demonstrated an increase in COX-2 expression but still do not demonstrate a fever at 4 h post-LPS. This time frame was not investigated by Inoue et al (34), and therefore, we are unable to make direct comparisons with their data. However, it may again indicate that the CR animals, in contrast to fasted animals, display a delayed inflammatory response at 4 h post-LPS.…”

Section: Cr Sickness Behavior and A Potential Mechanismmentioning

confidence: 83%

“…Others have investigated COX-2 mRNA levels 2 h after LPS in animals fasted for 48 h and found no difference from controls (34). The discrepancy between the fasted and CR animals may be due to the two different dietary regimens, which have been shown to induce slightly different changes in mRNA profiles in the hypothalamus (6,9).…”

Section: Cr Sickness Behavior and A Potential Mechanismmentioning

confidence: 99%

“…More recently, rats fasted for 48 h and then exposed to an injection of LPS demonstrated a significantly attenuated fever compared with ad libitum-fed controls (34). In addition to the attenuated fever, the rise in plasma levels of TNF-␣ and IL-1ra were attenuated; however, not all cytokine levels were reduced in fasted animals.…”

mentioning

confidence: 99%

“…In addition to the attenuated fever, the rise in plasma levels of TNF-␣ and IL-1ra were attenuated; however, not all cytokine levels were reduced in fasted animals. Interestingly, mRNA expression of IL-1␤, cyclooxygenase-2 (COX-2), and prostaglandin E 2 (PGE 2 ) in the hypothalamus of fasted animals exposed to LPS were at levels seen in ad libitum-fed animals injected with LPS (34).…”

mentioning

confidence: 99%

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Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

MacDonald

Radler

Paolini

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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MacDonald L, Radler M, Paolini AG, Kent S. Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias. Am J Physiol Regul Integr Comp Physiol 301: R172-R184, 2011. First published April 27, 2011 doi:10.1152/ajpregu.00057.2011 has been demonstrated to alter cytokine levels; however, its potential to modify sickness behavior (fever, anorexia, cachexia) has not. The effect of CR on sickness behavior was examined in male C57BL/6J mice fed ad libitum or restricted 25% (CR25%) or restricted 50% (CR50%) in food intake for 28 days and injected with 50 g/kg of LPS on day 29. Changes in body temperature, locomotor activity, body weight, and food intake were determined. A separate cohort of mice were fed ad libitum or CR50% for 28 days, and hypothalamic mRNA expression of inhibitory factor B-␣ (I B-␣), cyclooxygenase-2 (COX-2), prostaglandin E 2 (PGE2), suppressor of cytokine signaling 3 (SOCS3), IL-10, neuropeptide Y (NPY), leptin, proopiomelanocortin (POMC), and corticotrophin-releasing hormone (CRH) were determined at 0, 2, and 4 h post-LPS. CR50% mice did not develop fevers, whereas the CR25% mice displayed a fever shorter in duration but with the same peak as the controls. Both CR25% and CR50% mice showed no sign of anorexia and reduced cachexia after LPS administration. Hypothalamic mRNA expression of NPY and CRH were both increased by severalfold in CR50% animals preinjection compared with controls. The CR50% mice did not demonstrate the expected rise in hypothalamic mRNA expression of COX-2, microsomal prostaglandin E synthase-1, POMC, or CRH 2 h post-LPS, and leptin expression was decreased at this time point. Increases in SOCS3, IL-10, and I B-␣ expression in CR50% animals were enhanced compared with ad libitum-fed controls at 4 h post-LPS. CR results in a suppression of sickness behavior in a dose-dependent manner, which may be due to CR attenuating proinflammatory pathways and enhancing anti-inflammatory pathways. fever; suppressor of cytokine signaling 3; cyclooxygenase-2; microsomal prostaglandin E synthase-1; leptin CALORIE RESTRICTION (CR), a dietary regimen low in calories, while avoiding malnutrition, is the only manipulation that has consistently been shown to extend the mean and maximum life span in a range of species (2,42,71,76). In addition to an increase in life span, CR attenuates the normal immunosenscence seen with age (52), along with reducing the occurrence of other age-related diseases (14,39,43,53,54,79).It has been postulated that the mechanism by which CR extends the mean and maximum life span is by reducing oxidative stress caused by unregulated increases in reactive oxygen species (3,19,31,42,69), as well as by limiting the age-related increase in basal pro-inflammatory cytokine levels (73). One possible mechanism by which CR exerts its antiinflammatory effect are glucocorticoids, which are increased after CR (33, 47) and act to increase the transcription of anti-inflammatory cytokines and decrease the transcripti...

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Section: Cr and Sickness Behaviormentioning

confidence: 43%

Section: Cr Sickness Behavior and A Potential Mechanismmentioning

confidence: 83%

Section: Cr Sickness Behavior and A Potential Mechanismmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

MacDonald

Radler

Paolini

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Mechanisms of Fever Production and Lysis: Lessons from Experimental LPS Fever

Roth

Blatteis

2014

Comprehensive Physiology

155

117

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Fever is a cardinal symptom of infectious or inflammatory insults, but it can also arise from noninfectious causes. The fever-inducing agent that has been used most frequently in experimental studies designed to characterize the physiological, immunological and neuroendocrine processes and to identify the neuronal circuits that underlie the manifestation of the febrile response is lipopolysaccharide (LPS). Our knowledge of the mechanisms of fever production and lysis is largely based on this model. Fever is usually initiated in the periphery of the challenged host by the immediate activation of the innate immune system by LPS, specifically of the complement (C) cascade and Toll-like receptors. The first results in the immediate generation of the C component C5a and the subsequent rapid production of prostaglandin E2 (PGE2). The second, occurring after some delay, induces the further production of PGE2 by induction of its synthesizing enzymes and transcription and translation of proinflammatory cytokines. The Kupffer cells (Kc) of the liver seem to be essential for these initial processes. The subsequent transfer of the pyrogenic message from the periphery to the brain is achieved by neuronal and humoral mechanisms. These pathways subserve the genesis of early (neuronal signals) and late (humoral signals) phases of the characteristically biphasic febrile response to LPS. During the course of fever, counterinflammatory factors, "endogenous antipyretics," are elaborated peripherally and centrally to limit fever in strength and duration. The multiple interacting pro- and antipyretic signals and their mechanistic effects that underlie endotoxic fever are the subjects of this review.

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Tumour necrosis factor in infectious disease

Waters

Pober

Bradley

2013

The Journal of Pathology

117

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TNF signals through two distinct receptors, designated TNFR1 and TNFR2, which initiate diverse cellular effects that include cell survival, activation, differentiation, and proliferation and cell death. These cellular responses can promote immunological and inflammatory responses that eradicate infectious agents, but can also lead to local tissue injury at sites of infection and harmful systemic effects. Defining the molecular mechanisms involved in TNF responses, the effects of natural and experimental genetic diversity in TNF signalling and the effects of therapeutic blockade of TNF has increased our understanding of the key role that TNF plays in infectious disease.

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Immune-to-brain signaling and central prostaglandin E₂synthesis in fasted rats with altered lipopolysaccharide-induced fever

Abstract: Inoue W, Somay G, Poole S, Luheshi GN. Immune-to-brain signaling and central prostaglandin E2 synthesis in fasted rats with altered lipopolysaccharide-induced fever.

Cited by 40 publications

References 58 publications

Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

Mechanisms of Fever Production and Lysis: Lessons from Experimental LPS Fever

Tumour necrosis factor in infectious disease

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Immune-to-brain signaling and central prostaglandin E2synthesis in fasted rats with altered lipopolysaccharide-induced fever

Abstract: Inoue W, Somay G, Poole S, Luheshi GN. Immune-to-brain signaling and central prostaglandin E2 synthesis in fasted rats with altered lipopolysaccharide-induced fever.

Cited by 40 publications

References 58 publications

Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

Mechanisms of Fever Production and Lysis: Lessons from Experimental LPS Fever

Tumour necrosis factor in infectious disease

Contact Info

Product

Resources

About

Immune-to-brain signaling and central prostaglandin E₂synthesis in fasted rats with altered lipopolysaccharide-induced fever