Interleukin-8 induces fever by a prostaglandin-independent mechanism

Zampronio, Aleksander Roberto; Souza, Glória Emília Petto de; Silva, C. A. A.; Cunha, Fernando Q.; Ferreira, S. H.

doi:10.1152/ajpregu.1994.266.5.r1670

Cited by 63 publications

(75 citation statements)

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“…Alternatively, the endothelium of the cerebral vasculature may be the site where circulating cytokines or LPS could interact with receptors and stimulate the endothelial cells to release additional cytokines or other secondary mediators abluminally into the brain. For example, IL-6 (5-7), IL-8 (16) and MIP-1 (46) are produced and released within the brain in response to peripheral LPS and a central pyrogenic activity of these cytokines has been demonstrated (2,7,13,16,19,47). Especially, the appearance and biological action of IL-6 within the brain seem to be a critical component of fever generation as convincingly demonstrated in a study using IL-6-deficient (IL-6 knockout) mice (48).…”

Section: Final Fever-inducing Mediators In the Thermoregulatory Centementioning

confidence: 99%

“…It has been argued that the feverinducing properties of cytokines may rather represent pharmacological effects unrelated to LPS fever (2). Furthermore, it should be noted that only cytokines such as IL-6 which are circulating in large amounts during LPS fever are able to evoke moderate febrile responses (13), and that the pyrogenic effect does not manifest itself in all species of experimental animals as reported for IL-8 (14,16). However, the fact that cytokines circulating during LPS fever are themselves pyrogenic in most animal species still supports the hypothesis that these endogenous mediators can potentially act as humoral signals for the brain to induce fever and other sickness signs in response to infectious or inflammatory stimulation.…”

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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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Section: Final Fever-inducing Mediators In the Thermoregulatory Centementioning

confidence: 99%

mentioning

confidence: 99%

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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“…Taken together, these findings led us to propose that, similar to corticotropin-releasing hormone, macrophage inflammatory protein-1, preformed pyrogenic factor, and IL-8 (13,31,46,47), ET-1 may act as a mediator of a putative COX-independent pathway of fever triggered by LPS in rats (15).…”

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confidence: 93%

The effects of selective and nonselective cyclooxygenase inhibitors on endothelin-1-induced fever in rats

Fabricio

Veiga²,

Cristofoletti³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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It was previously shown that sustained fever can be induced in rats by central injection of endothelin-1 (ET-1). This peptide appears to participate in the mechanism(s) of LPS-induced fever, which is reduced by pretreatments with ET B receptor antagonists. In this study, we compared the effects of a nonselective cyclooxygenase (COX) inhibitor, indomethacin, with those of two selective COX-2 inhibitors, celecoxib and lumiracoxib, on ET-1-induced fever in rats. Fever induced in conscious animals by ET-1 (1 pmol icv) or LPS (5 g/kg iv) was prevented by pretreatments with celecoxib (5 and 10 mg/kg) or lumiracoxib (5 mg/kg) given by oral gavage 1 h before stimuli. Lower doses of celecoxib had partial (2.5 mg/kg) or no effect (1 mg/kg). Indomethacin (2 mg/kg ip) partially inhibited fever induced by LPS but had no effect on ET-1-induced fever. The levels of PGE2 and PGF2␣ in the cerebrospinal fluid (CSF) of pentobarbital sodium-anesthetized rats were significantly increased 3 h after the injection of LPS or ET-1. The latter increase was abolished by celecoxib at all tested doses and by indomethacin. In conclusion, selective COX-2 inhibitors were able to prevent ET-1-induced fever, indicating a role for COX-2 in this phenomenon. However, the fact that reduced CSF PG levels obtained with indomethacin and a low dose of celecoxib are not accompanied by changes in fever induced by ET-1, along with the lack of inhibitory effects of indomethacin on ET-1 fever, suggests that the latter might also involve COX-2-independent mechanisms.cyclooxygenase-2 inhibitors; indomethacin; prostaglandins; cerebrospinal fluid; lipopolysaccharide IT IS NOW WELL ESTABLISHED that the PGs represent the final mediators of fever induced by exogenous and endogenous pyrogens through an action on PG receptor-expressing neurons in the preoptic area (POA) of the anterior hypothalamus (33). In fact, PGE 2 induces fever when injected centrally (13,33,38), and its levels in the cerebrospinal fluid (CSF) and in the POA rise in parallel with the generation of fever caused by several stimuli (9,12,16,19,23,27,35,42). Moreover, the inhibition of PG synthesis by cyclooxygenase (COX) inhibitors attenuates fever in humans and experimental animals, whereas these drugs do not affect fever induced by the administration of PGs (4,7,12,13,37,39). PGF 2␣ also induces fever when injected centrally (13, 34), and its levels are increased in rat CSF in response to LPS (10).We have previously observed that endothelin-1 (ET-1), a member of the ET family of peptides (29), acts as a mediator of LPS-induced fever (15). In fact, intracerebroventricular (icv) pretreatment with the selective ET B receptor antagonist BQ-788 blunted fever induced by intravenous LPS or intracerebroventricular ET-1 (15). The rise in core temperature induced by intracerebroventricular ET-1 was accompanied by such thermoeffector response as cutaneous vasoconstriction, measured as a decrease in tail skin temperature (Fabricio, unpublished observation). The simultaneous occurrence of increased core temper...

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“…Uma outra classe de moléculas sintetizadas pelas células de defesa e que tem participação na resposta febril são as quimiocinas (Oppenheim et al, 1991;Horuk, 1994;Davatelis et al, 1989;Zampronio et al, 1994a, Melo Soares et al, 2006, Machado et al, 2007Soares et al, 2008). As quimiocinas são uma família de proteínas quimioatraentes de peso molecular entre 8 e 10 kDa (Luster, 1998) e que apresentam quatro resíduos de cisteína conservados formando duas pontes dissulfeto essenciais, possuem um curto domínio amino-terminal antecedendo a primeira cisteína, formando o grupo denominado CC ou α-quimiocinas; separadas por um aminoácido, denominado de CXC ou β-quimiocinas ou separadas por três aminoácidos, formando as CX3C quimiocinas.…”

Section: -Quimiocinasunclassified

“…A participação de quimiocinas na resposta febril foi evidenciada pela capacidade da interleucina-8 (IL-8) (Rothwell et al, 1990;Zampronio et al, 1994a), da família CXC, e proteína inflamatória derivada de macrófagos-1 (MIP-1α) (Davatelis et al, 1989;Miñano et al, 1990;Melo Soares et al, 2006), da família CC, induzirem resposta febril em coelhos e ratos.…”

Section: -Quimiocinasunclassified

Mediadores envolvidos na resposta febril induzida pela RANTES

Machado¹

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Interleukin-8 induces fever by a prostaglandin-independent mechanism

Cited by 63 publications

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

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

The effects of selective and nonselective cyclooxygenase inhibitors on endothelin-1-induced fever in rats

Mediadores envolvidos na resposta febril induzida pela RANTES

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