Humoral versus Neural Pathways for Fever Production in Rats after Administration of Lipopolysaccharide

Caldwell, Fred T.; Graves, Denise B.; Wallace, Bonny H.

doi:10.1097/00005373-199907000-00025

Cited by 28 publications

(26 citation statements)

References 13 publications

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“…In sham-vagotomized rats, the viscera were handled, but no nerves were cut. To alleviate the gastrointestinal complications of vagotomy, the vagotomized (but not sham-vagotomized) rats received a highly palatable liquid diet (PMI Micro-stabilized Rodent Liquid Diet LD101; TestDiet, Richmond, IN) for days [1][2][3][4][5][6][7][8][9]. Placing the animals on a liquid diet prevents excessive body mass loss and other complications of vagotomy (1,66,70) that are suspected to underlie some contradictory results of fever experiments in vagotomized animals (62).…”

Section: Experiments In Conscious Ratsmentioning

confidence: 99%

Fever response to intravenous prostaglandin E₂ is mediated by the brain but does not require afferent vagal signaling

Ootsuka¹,

Blessing²,

Steiner³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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PGE2 produced in the periphery triggers the early phase of the febrile response to infection and may contribute to later phases. It can be hypothesized that peripherally synthesized PGE2 transmits febrigenic signals to the brain via vagal afferent nerves. Before testing this hypothesis, we investigated whether the febrigenic effect of intravenously administered PGE2 is mediated by the brain and is not the result of a direct action of PGE2 on thermoeffectors. In anesthetized rats, intravenously injected PGE2 (100 microg/kg) caused an increase in sympathetic discharge to interscapular brown adipose tissue (iBAT), as well as increases in iBAT thermogenesis, end-expired CO2, and colonic temperature (Tc). All these effects were prevented by inhibition of neuronal function in the raphe region of the medulla oblongata using an intra-raphe microinjection of muscimol. We then asked whether the brain-mediated PGE2 fever requires vagal signaling and answered this question by conducting two independent studies in rats. In a study in anesthetized rats, acute bilateral cervical vagotomy did not affect the effects of intravenously injected PGE2 (100 microg/kg) on iBAT sympathetic discharge and Tc. In a study in conscious rats, administration of PGE2 (280 microg/kg) via an indwelling jugular catheter caused tail skin vasoconstriction, tended to increase oxygen consumption, and increased Tc; none of these responses was affected by total truncal subdiaphragmatic vagotomy performed 2 wk before the experiment. We conclude that the febrile response to circulating PGE2 is mediated by the brain, but that it does not require vagal afferent signaling.

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Section: Experiments In Conscious Ratsmentioning

confidence: 99%

Fever response to intravenous prostaglandin E₂ is mediated by the brain but does not require afferent vagal signaling

Ootsuka¹,

Blessing²,

Steiner³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…However, because the serotype of LPS was not reported, it is difficult to compare information regarding the precise dose with previous studies. Nonetheless, similar to Tb (12,43,63), these data suggest that vagal activation is necessary for the expression of anorexia after a low dose of LPS and that extravagal mechanisms are required following a high dose. With this in mind, central CCK 2 receptors are likely to mediate the anorexic effects of large doses of LPS, whereas smaller doses may activate either peripheral CCK 2 receptors of the vagus, and/or central CCK 2 receptors after vagal activation.…”

Section: Discussionmentioning

confidence: 60%

“…This is interesting with respect to a possible mechanism of action, as subdiaphragmatic VGX attenuates or abolishes LPS-and IL-1␤-induced fever when they are administered in low doses only (25,63). After high doses, VGX failed to prevent the induction of fever (2,12,43,63). This raises the possibility that, in response to high doses of LPS, CCK may act on CCK 2 receptors to induce the expression of fever via a central, nonvagal route.…”

Section: Discussionmentioning

confidence: 99%

“…A decrease in social interaction has been shown to depend upon the integrity of vagal afferents regardless of dose (10,11,36,43). Subdiaphragmatic VGX attenuated the fever and anorexia induced by a low, but not a high, dose of LPS (2,71,12,43,63). Thus the mechanisms of communication from the periphery to the brain, and their dose-dependence, differ for different components of the immune response.…”

Section: Discussionmentioning

confidence: 99%

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CCK₂receptor nullification attenuates lipopolysaccharide-induced sickness behavior

Weiland¹,

Voudouris²,

Kent³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Weiland, Tracey J., Nicholas J. Voudouris, and Stephen Kent. CCK2 receptor nullification attenuates lipopolysaccharide-induced sickness behavior. Am J Physiol Regul Integr Comp Physiol 292: R112-R123, 2007. First published July 20, 2006; doi:10.1152/ajpregu.00156.2006.-Systemic infection produces a highly regulated set of responses such as fever, anorexia, adipsia, inactivity, and cachexia, collectively referred to as sickness behavior. Although the expression of sickness behavior requires immune-brain communication, the mechanisms by which peripheral cytokines signal the brain are unclear. Several mechanisms have been proposed for neuroimmune communication, including the interaction of cytokines with peripheral nerves. A critical role has been ascribed to the vagus nerve in mediating sickness behavior after intraperitoneally delivered immune activation, and converging evidence suggests that this communication may involve neurochemical intermediaries afferent and/or efferent to this nerve. Mice lacking functional CCK 2/gastrin receptors (CCK2KO) and wild-type (WT) controls were administered LPS (50, 500, or 2,500 g/kg; serotype 0111:B4; ip). Results indicate a role for CCK2 receptor activation in the initiation and maintenance of LPS-induced sickness behavior. Compared with WT controls, CCK 2KO mice were significantly less affected by LPS on measures of body temperature, activity, body weight, and food intake, with the magnitude of effects increasing with increasing LPS dose. Although activation of CCK 2 receptors at the level of the vagus nerve cannot be excluded, a possible role for these receptors in nonvagal routes of immune-brain communication is suggested. cholecystokinin; lipopolysaccharide; infection; vagus; fever THE GUT-BRAIN PEPTIDE, CCK, exhibits great potential as a neurochemical intermediary of vagus-to-brain signaling. CCK binds to CCK 1 and CCK 2 receptors; the former are primarily localized in peripheral organs and some discrete areas of the brain, whereas CCK 2 receptors are the predominant subtype in the brain (55). Both subtypes are present on the vagus nerve and vagal afferent connections, including the brainstem and hypothalamus (46,51). Thus the peripheral and central positioning of CCK receptors provides an anatomical basis for CCK to play a role in vagally mediated neuroimmune communication.A constellation of findings points to a role for CCK in immune regulation, including a protective function in septic shock induced by LPS (41, 42), a compound of the outer cell wall of Gram-negative bacteria (60). CCK induces monocyte chemotaxis both in vitro and in vivo (16, 65) and stimulates production of proinflammatory cytokines, TNF, IL-1␤, IL-6, and IL-8 (16). Peripheral administration of CCK induces a pattern of c-fos expression that is similar to that seen after administration of the immune activators, LPS, or IL-1␤ (19). Increases in plasma CCK have been reported in the rat after intraperitoneal IL-1␣ (18) or intravenous IL-1␤ (40). However, limitations in assay sensitivity and specificity r...

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“…In the rat, there are about 11,000 nerve fibers in each of the subdiaphragmatic trunks, of which about 8,000 are afferent and 3,000 efferent, and are generally similar in human [17]. However, vagotomy itself has no marked effect on circulating endotoxin levels, and the production of IL-1β, IL-6, corticosterone, or adrenocorticotropic hormone after endotoxin challenge [18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Clinical influence of vagotomy on postoperative acute phase response

Fujita

Yanaga

2006

Langenbecks Arch Surg

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Humoral versus Neural Pathways for Fever Production in Rats after Administration of Lipopolysaccharide

Cited by 28 publications

References 13 publications

Fever response to intravenous prostaglandin E₂ is mediated by the brain but does not require afferent vagal signaling

Fever response to intravenous prostaglandin E₂ is mediated by the brain but does not require afferent vagal signaling

CCK₂receptor nullification attenuates lipopolysaccharide-induced sickness behavior

Clinical influence of vagotomy on postoperative acute phase response

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Humoral versus Neural Pathways for Fever Production in Rats after Administration of Lipopolysaccharide

Cited by 28 publications

References 13 publications

Fever response to intravenous prostaglandin E2 is mediated by the brain but does not require afferent vagal signaling

Fever response to intravenous prostaglandin E2 is mediated by the brain but does not require afferent vagal signaling

CCK2receptor nullification attenuates lipopolysaccharide-induced sickness behavior

Clinical influence of vagotomy on postoperative acute phase response

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Fever response to intravenous prostaglandin E₂ is mediated by the brain but does not require afferent vagal signaling

Fever response to intravenous prostaglandin E₂ is mediated by the brain but does not require afferent vagal signaling

CCK₂receptor nullification attenuates lipopolysaccharide-induced sickness behavior