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."
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA.
Zhonghua
Z
Li
Carlos
C
Feleder
Clark M
CM
Blatteis
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