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Afferent Pathways of Pyrogen Signaling a
Author(s) -
BLATTEIS CLARK M.,
SEHIC ELMIR,
LI SHUXIN
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb08318.x
Subject(s) - lipopolysaccharide , chemistry , complement system , prostaglandin , prostaglandin e2 , kupffer cell , prostaglandin e , alternative complement pathway , pharmacology , guinea pig , endocrinology , immunology , medicine , biochemistry , antibody
We and others recently showed that fever induced by intravenously or intraperitoneally injected lipopolysaccharide (LPS) may involve brain signaling via hepatic vagal afferents. This suggests that LPS fever may be initiated by mediators released mainly by cells in the liver, presumably macrophages (Kupffer cells, Kc). To verify this possibility, we disabled the Kc of conscious guinea pigs with gadolinium chloride and monitored their core temperature and associated preoptic prostaglandin E 2 (PGE 2 ) responses to iv LPS. Gadolinium chloride pretreatment significantly attenuated both the febrile and PGE 2 rises, thus supporting the hypothesis. Additionally, fluorescein‐labeled LPS was detected in Kc 15 minutes after its iv administration. Paradoxically, however, the label was also present in gadolinium chloride‐pretreated guinea pigs. Thus, either Kc are not the primary source of pyrogenic mediators or LPS does not provide the stimulus for their production. Because the iv injection of LPS elicits virtually immediately the production of complement fragments, and Kc express their receptors and produce various mediators on their activation, we hypocomplemented guinea pigs with cobra venom factor. The core temperature rises produced by iv LPS were reduced by complement depletions >60%. LPS iv per se decreased complement, that is, complement was consumed by 12% within 10 minutes. Thus, the onset of LPS fever may involve complement system and Kc activation, but their precise roles await clarification.