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Am J Physiol Regul Integr Comp Physiol 284: R1466-R1476, 2003. First published March 6, 2003; doi:10.1152/ajpregu.00378.2002
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Vol. 284, Issue 6, R1466-R1476, June 2003

The spleen modulates the febrile response of guinea pigs to LPS

Carlos Feleder, Zhonghua Li, Vit Perlik, Allison Evans, and Clark M. Blatteis

Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163

The febrile responses of splenectomized (Splex) or sham-operated (Sham) guinea pigs challenged intravenously or intraperitoneally with lipopolysaccharide (LPS) 7 and 30 days after surgery were evaluated. FITC-LPS uptake by Kupffer cells (KC) was additionally assessed 15, 30, and 60 min after injection. LPS at 0.05 µg/kg iv did not evoke fever in Sham animals but caused a 1.2°C core temperature (Tc) rise in the Splex animals. LPS at 2 µg/kg iv induced a 1.8°C greater Tc rise of the Splex animals than of their controls. LPS at 2 and 8 µg/kg ip 7 days postsurgery induced 1.4 and 1.8°C higher fevers, respectively, in the Splex than Sham animals. LPS at 2 and 8 µg/kg ip 30 days postsurgery also increased the febrile responses of the asplenic animals by 1.6 and 1.8°C, respectively. FITC-LPS at 7 days was detected in the controls within KC 15 min after its administration; the label density was reduced at 30 min and almost 0 at 60 min. In the Splex group, in contrast, the labeling was significantly denser and remained unchanged through all three time points; this effect was still present 30 days after surgery. Similar results were obtained at 60 min after FITC-LPS intraperitoneal injection. Gadolinium chloride pretreatment (-3 days) of the Splex group significantly reduced both their febrile responses to LPS (8 µg/kg ip) and their KC uptake of FITC-LPS 7 days postsurgery. Thus splenectomy increases the magnitude of the febrile response of guinea pigs and the uptake of systemically administered LPS.

fever; splenectomy; Kupffer cells; fluorescein isothiocyanate-lipopolysaccharide


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