Lipopolysaccharide challenge causes exaggerated fever and increased hepatic lipopolysaccharide uptake in vinblastine-induced leukopenic guinea pigs.
OBJECTIVE
To better understand the pathophysiology of the fever often manifested by immunocompromised patients undergoing chemotherapy that become neutropenic and suffer a bacterial infection.


METHODS
Prospective animal study.


METHODS
A physiology laboratory in a medical school setting.


RESULTS
We induced leukopenia in guinea pigs with vinblastine (0.7 mg/kg, intravenously, 4 days before) and measured the animals' febrile response to 2 microg of lipopolysaccharide/kg and the uptake of 75 microg of fluorescein isothiocyanate-labeled lipopolysaccharide/kg by Kupffer cells. The leukopenic animals exhibited significantly higher fevers and greater hepatic fluorescein isothiocyanate-lipopolysaccharide uptake than their controls.


CONCLUSIONS
Lipopolysaccharide-challenged, vinblastine-induced leukopenic guinea pigs exhibit hyperpyrexia and significantly elevated uptake of lipopolysaccharide by Kupffer cells, the major source of pyrogenic mediators. This could explain "febrile neutropenia."
Li
Zhonghua
Z
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA.
Feleder
Carlos
C
Blatteis
Clark M
CM
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects; D005334:Fever / Q000209:etiology / Q000276:immunology*; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D007728:Kupffer Cells / Q000276:immunology; D007970:Leukopenia / Q000139:chemically induced / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008297:Male; D011446:Prospective Studies; D014747:Vinblastine / Q000009:adverse effects
D000972:Antineoplastic Agents, Phytogenic; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D014747:Vinblastine; D016650:Fluorescein-5-isothiocyanate