title: Blockade of lipopolysaccharide-induced fever by subdiaphragmatic vagotomy in guinea pigs.
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. PGE2 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 (Tc) following the intravenous (i.v.) 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 micrograms/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; Tc was monitored continuously using thermocouples inserted 5 cm into the colon. LPS induced a biphasic fall in Tc 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 preopitc PGE2 and Tc 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.
authors.affiliation: Department of Physiology and Biophysics, University of Tennessee Health Sciences Center, Memphis 38163, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sehic
authors.forename: C M
authors.initials: CM
authors.lastname: Blatteis
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D003964:Diaphragm; D015232:Dinoprostone / Q000096:biosynthesis*; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008297:Male; D017551:Microdialysis; D011301:Preoptic Area / Q000187:drug effects* / Q000378:metabolism; D011749:Pyrogens / Q000037:antagonists & inhibitors*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D011749:Pyrogens; D015232:Dinoprostone