Relation between complement and the febrile response of guinea pigs to systemic endotoxin

Li, S.; Sehic, Elmir; Wang, Y.; Ungar, A. L.; Blatteis, Clark M.

doi:10.1152/ajpregu.1999.277.6.r1635

Cited by 19 publications

(46 citation statements)

References 37 publications

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“…To verify a posteriori whether KC in particular were the cell types that bound FITC-LPS and accounted for the associated Tc changes observed in this study, Sham and Splex guinea pigs were injected 7 days postoperatively with 75 g FITC-LPS/kg ip, 3 days after the intravenous injection (in the penile vein, under light metofane anesthesia) of 7.5 mg GdCl 3/kg (21). The animals were killed 60 min after the FITC-LPS injection and perfused transcardially, their livers were excised and processed, and the fluorescent patches were counted as before.…”

Section: Experiments 2: Effects Of Intraperitoneal Lps On T Cmentioning

confidence: 98%

The spleen modulates the febrile response of guinea pigs to LPS

Feleder

Perlik

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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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.

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Section: Experiments 2: Effects Of Intraperitoneal Lps On T Cmentioning

confidence: 98%

The spleen modulates the febrile response of guinea pigs to LPS

Feleder

Perlik

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The proposed pathway of how sensory nerves, namely afferents of the vagus nerve, transmit signals to the relevant hypothalamic areas has been recently described (3,20) and can be summarized as follows. The appearance of LPS in the bloodstream leads to a rapid complement activation within minutes.…”

Section: Entry Of Humoral or Neural Signals Into The Brainmentioning

confidence: 99%

“…The signals of hepatic vagal afferents are transported to the central projection areas of the vagus nerve within the nucleus of the solitary tract. The pyrogenic message is then passed to the noradrenergic A1/A2 cell groups which are located in this brainstem area and project directly to preoptic and hypothalamic areas via the ventral noradrenergic bundle (for further details of this hypothesis, see 3,20).…”

Section: Entry Of Humoral or Neural Signals Into The Brainmentioning

confidence: 99%

“…One possibility which has been discussed in this context is the existence of a preformed pyrogenic factor (PFPF) which is continuously present in macrophages and can be released immediately after LPS stimulation (19). Also, pyrogenic substances which can be induced by LPS within seconds or minutes such as complement fragments have been proposed as endogenous humoral signals for induction of the early phase of fever (3,20). Finally, it has been (22).…”

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confidence: 99%

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Fever induction pathways: evidence from responses to systemic or local cytokine formation

Roth

Souza

2001

Braz J Med Biol Res

176

114

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The immune and central nervous systems are functionally connected and interacting. The concept that the immune signaling to the brain which induces fever during infection and inflammation is mediated by circulating cytokines has been traditionally accepted. Administration of bacterial lipopolysaccharide (LPS) induces the appearance of a sotermed cytokine cascade in the circulation more or less concomitantly to the developing febrile response. Also, LPS-like fever can be induced by systemic administration of key cytokines (IL-1ß, TNF-a, and others). However, anti-cytokine strategies against IL-1ß or TNFa along with systemic injections of LPS frequently lead to attenuation of the later stages of the febrile response but not of the initial phase of fever, indicating that cytokines are rather involved in the maintenance than in the early induction of fever. Within the last years experimental evidence has accumulated indicating the existence of neural transport pathways of immune signals to the brain. Because subdiaphragmatic vagotomy prevents or attenuates fever in response to intraperitoneal or intravenous injections of LPS, a role for vagal afferent nerve fibers in fever induction has been proposed. Also other sensory nerves may participate in the manifestation of febrile responses under certain experimental conditions. Thus, injection of a small dose of LPS into an artificial subcutaneous chamber results in fever and formation of cytokines within the inflamed tissue around the site of injection. This febrile response can be blocked in part by injection of a local anesthetic into the subcutaneous chamber, indicating a participation of cutaneous afferent nerve signals in the manifestation of fever in this model. In conclusion, humoral signals and an inflammatory stimulation of afferent sensory nerves can participate in the generation and maintenance of a febrile response. Key wordsHumoral signals and fever: the relation between circulating cytokines and the febrile response After a challenge with an infectious or inflammatory stimulus somewhere at the periphery of the body a number of responses are generated within the CNS. These brainmediated signs of illness include changes in neuroendocrine activities including activation of the hypothalamic-pituitary-adrenal (HPA) axis, anorexia and adipsia, changes in

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“…LPS and because i.p. LPS per se promoted serum complement consumption (20,38). However, it was not determined in those studies which specific component(s) of the complement cascade may be especially critical in this regard, because CVF activates the whole alternative pathway (8,47) and the consequent serum complement level changes were assessed as the total hemolytic activity of complement.…”

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confidence: 99%

Modulation of Mouse Endotoxic Fever by Complement

Holers

Boackle

et al. 2002

Infect Immun

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It was recently reported that the complement system may be critically involved in the febrile response of guinea pigs to systemic, particularly intraperitoneally (i.p.) injected, lipopolysaccharides (LPS). The present study was designed to identify which component(s) of the complement cascade may be specifically critical. To this end, we used mice with C3, C5, and CR2 gene deletions. To assess preliminarily the suitability of mice for such a study, we replicated our earlier studies with guinea pigs. Thus, to verify initially whether complement is similarly involved in the febrile response of wild-type (C57BL/6J) mice to i.p. LPS (Escherichia coli, 1 g/mouse), we depleted complement with cobra venom factor (CVF; 7 U/mouse, intravenously [i.v.]). These animals did not develop fever, whereas the core temperature (T c ) of CVF vehicle-treated controls rose ϳ1°C by 80 min postinjection and then gradually abated over the following 2.5 h, confirming the involvement of complement in fever production after i.p. LPS injection and the suitability of this species for these studies. C3-and C5-sufficient (C3 ؉/؉ and C5 ؉/؉ ) mice also developed 1°C fevers within 80 min after i.p. LPS (1 or 2 g/mouse) injection. These fevers were totally prevented by CVF (10 U/mouse, i.v.) pretreatment. C3-and C5-deficient (C3 ؊/؊ and C5 ؊/؊ ) mice were also unable to develop T c rises after i.p. LPS. Both CR2 ؉/؉ and CR2 ؊/؊ mice responded normally to i.p. LPS (1 g/mouse). These data indicate that C5, but not C3d acting through CR2, may play a critical role in the febrile response of mice to i.p. LPS.

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Relation between complement and the febrile response of guinea pigs to systemic endotoxin

Cited by 19 publications

References 37 publications

The spleen modulates the febrile response of guinea pigs to LPS

The spleen modulates the febrile response of guinea pigs to LPS

Fever induction pathways: evidence from responses to systemic or local cytokine formation

Modulation of Mouse Endotoxic Fever by Complement

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