Fever produced by intrahypothalamic injection of interleukin-1 and interleukin-6

Lesnikov, Vladimir; Efremov, O. M.; Корнева, Е. А.; Damme, J. Van; Billiau, Alfons

doi:10.1016/1043-4666(91)90016-7

Cited by 33 publications

(20 citation statements)

References 13 publications

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“…(d) Solitery i.h. application of IL-6 induces a steadily increase in body temperature, lasting more than 6 h (Sakata et al, 1991;Lesnikov et al, 1991;Vybı´ral, unpublished), which contrasts with changes in body temperature induced by endotoxin.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Pyrogenic effects of cytokines (IL-1β, IL- 6, TNF-α) and their mode of action on thermoregulatory centers and functions

Vybíral

Bárczayová

Pešanová

et al. 2005

Journal of Thermal Biology

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Section: Discussionmentioning

confidence: 91%

“…Their central effect on hypothalamic thermoregulatory centers has been also studied intensively (IL-1b: Dascombe et al, 1989;Lesnikov et al, 1991;Busbridge et al, 1993;IL-6: Opp et al, 1989;Lemay et al, 1990b;Lesnikov et al, 1991;Sakata et al, 1991;Klir et al, 1993;TNF-a: Rothwell, 1988, Klir et al, 1993.…”

Section: Discussionmentioning

confidence: 98%

Pyrogenic effects of cytokines (IL-1β, IL- 6, TNF-α) and their mode of action on thermoregulatory centers and functions

Vybíral

Bárczayová

Pešanová

et al. 2005

Journal of Thermal Biology

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“…1-3). The biphasic nature of the fever responses to LPS (11) and IL-1 (10,19), which present a rapid rise followed by a second peak, has been described. Whereas PGE2 synthesis inhibitors block the long-lasting fever, the nature of the pyrogen responsible for the first phase of the response remained unknown.…”

Section: Discussionmentioning

confidence: 99%

Ceramide mediates the rapid phase of febrile response to IL-1β

Sanchez‐Alavez

Tabarean

Behrens

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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IL-1␤ was identified after a long search for the endogenous pyrogen. It acts by inducing synthesis of prostaglandin E 2, which mediates the late phase of IL-1␤-induced fever. Here we show by radiotelemetry that the early phase of the fever response to IL-1␤ is mediated by ceramide. Hypothalamic application of the cellpenetrating C2-ceramide mimics the rapid phase of the IL-1␤-induced fever. Inhibition of ceramide synthesis blocks the rapid phase of fever but does not affect the slower prostaglandin E 2-dependent phase, which is blocked by indomethacin or by null mutation of the EP3 prostanoid receptor. Electrophysiological experiments on preoptic area͞anterior hypothalamic neurons show that C2-ceramide, but not dihydroceramide, mimics the rapid hyperpolarizing effects of IL-1␤ on the activity of warm-sensitive hypothalamic neurons. IL-1␤-mediated hyperpolarization is blocked by PP2, the selective inhibitor of the protein tyrosine kinase Src, which is known to be activated by ceramide. These in vivo and in vitro data suggest that ceramide fulfills the criteria for an endogenous pyrogen.fever ͉ neutral sphingomyelinase ͉ preoptic area A multitude of microbial and inorganic substances of widely varying origin and chemical composition are able to cause fever, a regulated rise in core body temperature (CBT) (1, 2). Root and Wolff (3) have pointed out that the uniformity of the fever response to all of these pyrogens, with respect to peak temperature and duration, suggests there may be an endogenous common mediator, an endogenous pyrogen. A long search has identified IL-1 as the endogenous pyrogen that mediates the common action of a broad variety of exogenous substances (4). Another line of investigation for the endogenous pyrogens was based on the pharmacological identification of antipyretic substances such as salicylates more than a century ago. Because this class of antipyretic agents are effective in reducing fever of almost any cause, it was implied there must exist an endogenous pyrogen whose synthesis and͞or effects are blocked by salicylates. Experiments with purified and later with recombinant IL-1␤ showed that indeed the fever response to LPS, an exogenous pyrogen from Gram-negative bacteria wall, was mimicked by IL-1␤ (reviewed in ref. 1) and blocked by salicylates (5). The identification of prostaglandin (PG) E 2 (PGE2) as another endogenous pyrogen and the recognition of the role of salicylates and aspirin-like antiinflammatory drugs as inhibitors of PG biosynthesis have produced a working hypothesis for the fever response to Gram-negative bacteria: Bacterial cell wall 3 LPS 3 IL-1␤ 3 cyclooxygenase (COX)2 3 PGE2 3 fever response.This cascade also provided an explanation for the antipyretic effects of PG synthesis inhibitors. Subsequent studies using null mutated mice strains for prostanoid receptor subtypes, as well as selective drugs for prostanoid receptors, identified the EP3 prostanoid receptor (EP3R) and EP1R receptors as mediators of the pyrogenic effects of PGE2 (6-9). This scheme has been usefu...

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“…Ample evidence exists in the literature suggesting that interleukin (IL)-1, tumor necrosis factor (TNF) alpha, and IL-6-inflammatory cytokines that are initially released from the site of infection-are present in the circulation during infection [9]. In addition, intravenous administration of these cytokine induces CNS-controlled sickness symptoms similar to those observed during infection [10][11][12][13]. Therefore, circulating cytokines were considered the messengers for immune-to-brain signaling.…”

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confidence: 96%

Immune-To-Brain Signaling: How Important are the Blood–Brain Barrier-independent Pathways?

Quan

2008

Mol Neurobiol

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A conceptual obstacle for understanding immune-to-brain signaling is the issue of the blood-brain barrier (BBB). In the last 30 years, several pathways have been investigated to address the question of how peripheral immune signals are transmitted into the brain. These pathways can be categorized into two types: BBB-dependent pathways and BBB-independent pathways. BBB-dependent pathways involve the BBB as a relay station or porous barrier, whereas BBB-independent pathways use neuronal routes that bypass the BBB. Recently, a complete BBB-dependent ascending pathway for immune-to-brain signaling has been described. Details of BBB-independent pathways are still under construction. In this review, I will summarize the current progress in unraveling immune-to-brain signaling pathways. In addition, I will provide a critical analysis of the literature to point to areas where our knowledge of the immunological afferent signaling to the central nervous system is still sorely lacking.

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Fever produced by intrahypothalamic injection of interleukin-1 and interleukin-6

Cited by 33 publications

References 13 publications

Pyrogenic effects of cytokines (IL-1β, IL- 6, TNF-α) and their mode of action on thermoregulatory centers and functions

Pyrogenic effects of cytokines (IL-1β, IL- 6, TNF-α) and their mode of action on thermoregulatory centers and functions

Ceramide mediates the rapid phase of febrile response to IL-1β

Immune-To-Brain Signaling: How Important are the Blood–Brain Barrier-independent Pathways?

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