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."