Role of interleukin 6 in fever in rats

LeMay, Lin G.; Vander, Arthur J.; Kluger, Matthew J.

doi:10.1152/ajpregu.1990.258.3.r798

Cited by 138 publications

(114 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…min IL-1J3 significantly increased rectal temperature at a dose of 300 pg, but at the same dose induced no significant change in the release of NA in the PVN. These results suggest that the release of NA in the PVN is not necessarily related to thermogenesis, and are compatible with findings that both IL-6 and tumor necrosis factor-a induce fever without affecting hypothalamic NA turnover [2, 20,21]. IL-1 is thought to increase body temperature through the production of prostaglandin E2 [22].…”

Section: Discussionsupporting

confidence: 87%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 87%

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

View full text Add to dashboard Cite

show abstract

“…In addition to sleep and other complex behavior, IL-1 and IL-6 have been implicated in the initiation of febrile responses to immune challenge [e.g., (LeMay et al, 1990;Rothwell et al, 1991;Kozak et al, 1998)]. Of importance to this present study, low doses of LPS administered intraperitoneally (IP) do not induce fever in IL-6 KO mice (Kozak et al, 1998;Zetterstrom et al, 1998;Morrow and Opp, 2005a).…”

Section: Introductionmentioning

confidence: 87%

Effects of i.c.v. administration of interleukin-1 on sleep and body temperature of interleukin-6-deficient mice

Olivadoti

Opp

2008

Neuroscience

View full text Add to dashboard Cite

Cytokines in brain contribute to the regulation of physiological processes and complex behavior, including sleep. The cytokines that have been most extensively studied with respect to sleep are interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6. Administration of these cytokines into laboratory animals, or in some cases into healthy human volunteers, increases the amount of time spent in non-rapid eye movement (NREM) sleep. Although antagonizing the IL-1 or TNF systems reduces the amount of time laboratory animals spend in NREM sleep, interactions among these three cytokine systems as they pertain to the regulation of physiological NREM sleep are not well understand. To further elucidate mechanisms in brain by which IL-1β, TNFα, and/or IL-6 contribute to NREM sleep regulation, we injected recombinant murine IL-1β (muIL-1β) into C57BL/6J mice and into IL-6-deficient mice (IL-6 knockout, KO). IL-6 KO (B6.129S6-Il6 tm1Kopf ; n = 13) and C57BL/6J mice (n = 14) were implanted with telemeters to record the electroencephalogram (EEG) and core body temperature, as well as with indwelling guide cannulae targeted to one of the lateral ventricles. After recovery and habituation, mice were injected intracerebroventricularly (ICV) just prior to dark onset on different days with either 0.5 µl vehicle (pyrogen-free saline; PFS) or with 0.5 µl PFS containing one of four doses of muIL-1β (2.5 ng, 5 ng, 10 ng, 50 ng). No mouse received more than two doses of muIL-1β, and administration of muIL-1β doses was counter-balanced to eliminate potential order effects. Sleep-wake behavior was determined for 24 h after injections. ICV administration of muIL-1β increased in NREM sleep of both mouse strains in a dose-related fashion, but the maximal increase was of greater magnitude in C57Bl/6J mice. muIL-1β induced fever in C57Bl/6J mice but not in IL-6 KO mice. Collectively, these data demonstrate IL-6 is necessary for IL-1 to induce fever, but IL-6 is not necessary for IL-1 to alter NREM sleep.

show abstract

“…SOCS3 acts to inhibit the production of IL-6 and aids in IL-10's anti-inflammatory properties [for example, suppressing the release of TNF-␣ (7)] and has been suggested to induce the expression of IL-1ra (5). It has been established that of all the proinflammatory cytokines, IL-6 most closely correlates with the magnitude of fever (11,44), and it has been demonstrated that IL-6 deficiency or treatment with IL-6 anti-serum can almost completely block fever induced by LPS (63). Even more interesting in light of our findings is that IL-6 can directly induce COX-2 expression in the brain (63), which in our study was attenuated at 2 h post-LPS compared with the AL animals.…”

Section: Cr Sickness Behavior and A Potential Mechanismmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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...

show abstract

Role of interleukin 6 in fever in rats

Cited by 138 publications

References 0 publications

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

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

Effects of i.c.v. administration of interleukin-1 on sleep and body temperature of interleukin-6-deficient mice

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

Contact Info

Product

Resources

About