The spleen modulates the febrile response of guinea pigs to LPS

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 mug/kg iv did not evoke fever in Sham animals but caused a 1.2degreesC core temperature (T-c) rise in the Splex animals. LPS at 2 mug/kg iv induced a 1.8 degreesC greater T-c rise of the Splex animals than of their controls. LPS at 2 and 8 mug/kg ip 7 days postsurgery induced 1.4 and 1.8 degreesC higher fevers, respectively, in the Splex than Sham animals. LPS at 2 and 8 mug/kg ip 30 days postsurgery also increased the febrile responses of the asplenic animals by 1.6 and 1.8 degreesC, 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 mug/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.