Blockade of lipopolysaccharide-induced fever by subdiaphragmatic vagotomy in guinea pigs

doi:10.1016/0006-8993(96)00326-5

Brain Research

Volume 726, Issues 1–2, 8 July 1996, Pages 160-166

https://doi.org/10.1016/0006-8993(96)00326-5 Get rights and content

Abstract

It is generally believed that fever is mediated by certain cytokines produced by immune cells activated by exogenous pyrogens, e.g., lipopolysaccharides (LPS), released into the circulation and transported to the brain. There, the cytokines are thought to stimulate prostaglandin (PG) E₂ production within the organum vasculosum laminae terminalis region. PGE, then may act as a febrigenic mediator locally or in the surrounding preoptic area (POA). However, whereas the increases in preoptic PGE₂ and body (core) temperature (T_c) following the intravenous (i.0 administration of LPS correlate temporally, cytokine levels in blood lag both these increases. From recent data in the literature, we have conjectured that a possible, alternative communication pathway between the i.v. LPS-activated immune system and brain PGE₂ may be provided by the vagi. To test this possibility, we measured the levels of PGE₂ in the extracellular fluid of the POA (collected by microdialysis) of conscious, subdiaphragmatically vagotomized or sham-operated guinea pigs following LPS administration (2 μg/kg; i.v.); controls received pyrogen-free saline (PFS). The effluents from the microdialysis probes were collected over 30-min periods throughout the experiments and the samples analyzed by radioimmunoassay; (T_c) was monitored continuously using thermocouples inserted 5 cm into the colon. LPS induced a biphasic fall in T_c and failed to increase preoptic PGE₂ levels in the vagotomized guinea pigs (n = 10), whereas in their sham-operated controls (n = 10) it induced increases in both preoptic PGE₂ and (T_c) within 15 min after its injection; PFS (n = 13) had no effect on either variable. We postulate that peripheral immune cell-derived signals may be transmitted via the vagi to the medulla. From other data, we suggest further that they may be conveyed from here via the ventral noradrenergic bundle to the POA region, where the released norepinephrine induces the local synthesis of PGE₂ and, hence, fever onset.

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Blockade of lipopolysaccharide-induced fever by subdiaphragmatic vagotomy in guinea pigs

Abstract

Neurosci. Lett.

Eur. J. Pharmacol.

Blood

Brain Res.

Brain Res. Bull.

Prostaglandins

Brain Res. Bull.

J. Neuroimmunol.

Neurosci Lett.

Gastroenterology

Brain Res. Bull.

Brain Res.

Bacterial lipopolysaccharides prime macrophages for enhanced release of arachidonic acid metabolites

J. Exp. Med.

Prostaglandins and fever: facts and controversies

Prostanoids and their receptors

Interleukin-1 receptors in the brain and endocrine tissues

Immunol. Today

Biologically active products of stimulated liver macrophages (Kupffer cells)

Eur. J. Biochem.

Selective depletion of macrophages prevents increased plasma interleukin-1 concentrations and pituitaryadrenal activation in response to endotoxin administration in rats

Endocrinology

Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: comparsion with interleukin-1

J. Pharmacol. Exp. Ther.

Anatomic characterization of the ventral medial peroptic area: involvement in the febrile reaction

Soc. Neurosci. Abst.

A functional anatomical analysis of central pathways subserving the effects of interleukin-1 on stress-related neuroendocrine neurons

J. Neurosci.

Fever, tumor necrosis factor and interleukin-6 in young, mature and aged, Fischer 344 rats

Am. J. Physiol.

Subdiaphragmatic vagotomy suppresses endotoxin-induced activation of hypothalamic corticotropin-releasing hormone neurons and ACTH secretion

Endocrinology