Putative antihyperpyretic factor induced by LPS in spleen of guinea pigs.
We reported previously that the onset of LPS-induced fever, irrespective of its route of administration, is temporally correlated with the appearance of LPS in the liver and that splenectomy significantly increases both the febrile response to LPS and the uptake of LPS by Kupffer cells (KC). To further evaluate the role of the spleen in LPS fever production, we ligated the splenic vein and, 7 and 30 days later, monitored the core temperature changes over 6 h after intraperitoneal (ip) injection of LPS (2 microg/kg). Both the febrile response and the uptake of LPS by KC were significantly augmented. Like splenectomy, splenic vein ligation (SVL) increased the febrile response and LPS uptake by KC until the collateral circulation developed, suggesting that the spleen may normally contribute an inhibitory factor that limits KC uptake of LPS and thus affects the febrile response. Subsequently, to verify the presence of this factor, we prepared splenic extracts from guinea pigs pretreated with LPS (8 microg/kg ip) or pyrogen-free saline, homogenized and ultrafiltered them, and injected them intravenously into splenectomized (Splex) guinea pigs pretreated with LPS (8 microg/kg ip). The results confirmed our presumption that the splenic extract from LPS-treated guinea pigs inhibits the exaggerated febrile response and the LPS uptake by the liver of Splex guinea pigs, indicating the presence of a putative splenic inhibitory factor, confirming the participation of the spleen in LPS-induced fever, and suggesting the existence of a novel antihyperpyretic mechanism. Preliminary data indicate that this factor is a lipid.
Feleder
Carlos
C
Dept. of Physiology, University of Tennessee Health Sciences Center, 894 Union Ave., Memphis, TN 38163, USA.
Perlik
Vit
V
Tang
Ying
Y
Blatteis
Clark M
CM
D018712:Analgesics, Non-Narcotic / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D007728:Kupffer Cells / Q000378:metabolism; D008026:Ligation; D008055:Lipids / Q000032:analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D011506:Proteins / Q000032:analysis; D013154:Spleen / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013162:Splenic Vein; D014020:Tissue Extracts / Q000737:chemistry / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D005456:Fluorescent Dyes; D008055:Lipids; D008070:Lipopolysaccharides; D011506:Proteins; D014020:Tissue Extracts; D016650:Fluorescein-5-isothiocyanate