title: Fever onset is linked to the appearance of lipopolysaccharide in the liver.
abstract: To assess the relative contributions of different phagocytes to the febrile response of guinea pigs to intravenous (i.v.) and intraperitoneal (i.p.) bacterial endotoxic lipopolysaccharide (LPS), we injected fluorescein isothiocyanate (FITC)-labeled LPS at doses of 37.5, 75, 150, 300 and 900 microg/kg, and measured its distribution and corresponding core temperature (T(c)) changes before and at 15, 30, 60, 90, and 120 min after injection. At all times, i.v. FITC-LPS appeared as granular fluorescent patches in circulating leukocytes and hepatic macrophages; its density was proportional to dose. At all doses, the density of i.v. FITC-LPS labeling decreased from its peak 15 min after injection at a rate commensurate with its dose. Intraperitoneal FITC-LPS was also present dose- and time-dependently in peritoneal macrophages, but it appeared later and accumulated more slowly except at the highest dose. Compared with i.v. FITC-LPS, its maximal appearance was always lower in density. No labeling was found at any time in brain and kidney following any dose of i.v. or i.p. FITC-LPS injection. The initiation of T(c) rises was best correlated with the presence of FITC-LPS in liver, irrespective of its route of injection. Pretreatment with gadolinium chloride 3 days before LPS injection attenuated the febrile response and reduced FITC-LPS labels in liver. These results suggest that the Kupffer cells may be central to the initiation of the febrile response of guinea pigs to i.v. and i.p. LPS.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Li
authors.forename: Clark M
authors.initials: CM
authors.lastname: Blatteis
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000209:etiology*; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D007728:Kupffer Cells / Q000502:physiology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D008099:Liver / Q000473:pathology*; D008297:Male
chemical_list: D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D016650:Fluorescein-5-isothiocyanate