Essential role for endothelin ET<sub>B</sub> receptors in fever induced by LPS (<i>E. coli</i>) in rats

Fabricio, Aline S C; Silva, Carlos A. A.; Rae, Giles A.; D’Orléans-Juste, Pedro; Souza, Glória Emília Petto de

doi:10.1038/sj.bjp.0702075

Cited by 52 publications

(51 citation statements)

References 55 publications

(60 reference statements)

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“…In our laboratory, it was shown that ␣-helical CRF 9 -41 antagonist (dual CRF 1 / CRF 2 receptor antagonist) blocks the fever induced by MIP-1␣ (Soares DM and Souza GE, unpublished observations), suggesting that the fever induced by this chemokine depends on CRF, which possibly recruits the opioidergic system. Fabricio et al (25) demonstrated that intracerebroventricular administration of ET-1 or intravenous administration of LPS induced an ET B , but not ET A , receptor-dependent increase in T b . We demonstrated in this study that the fever induced by ET-1 was completely abolished by this antagonist, suggesting that ET-1 subsequently would induce endogenous opioid release.…”

Section: Discussionmentioning

confidence: 99%

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Fraga

Machado²,

Fernandes³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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This study evaluated the participation of -opioid-receptor activation in body temperature (T b) during normal and febrile conditions (including activation of heat conservation mechanisms) and in different pathways of LPS-induced fever. The intracerebroventricular treatment of male Wistar rats with the selective opioid -receptor-antagonist cyclic D-Phe-Cys-Try-DTrp-Arg-Thr-Pen-Thr-NH2 (CTAP; 0.1-1.0 g) reduced fever induced by LPS (5.0 g/kg) but did not change Tb at ambient temperatures of either 20°C or 28°C. The subcutaneous, intracerebroventricular, and intrahypothalamic injection of morphine (1.0 -10.0 mg/kg, 3.0 -30.0 g, and 1-100 ng, respectively) produced a dose-dependent increase in Tb. Intracerebroventricular morphine also produced a peripheral vasoconstriction. Both effects were abolished by CTAP. CTAP (1.0 g icv) reduced the fever induced by intracerebroventricular administration of TNF-␣ (250 ng), IL-6 (300 ng), CRF (2.5 g), endothelin-1 (1.0 pmol), and macrophage inflammatory protein (500 pg) and the first phase of the fever induced by PGF2␣ (500.0 ng) but not the fever induced by IL-1␤ (3.12 ng) or PGE2 (125.0 ng) or the second phase of the fever induced by PGF2␣. Morphine-induced fever was not modified by the cyclooxygenase (COX) inhibitor indomethacin (2.0 mg/kg). In addition, morphine injection did not induce the expression of COX-2 in the hypothalamus, and CTAP did not modify PGE2 levels in cerebrospinal fluid or COX-2 expression in the hypothalamus after LPS injection. In conclusion, our results suggest that LPS and endogenous pyrogens (except IL-1␤ and prostaglandins) recruit the opioid system to cause a -receptor-mediated fever. prostaglandin independent; body temperature; morphine; CTAP THE REGULATION OF BODY TEMPERATURE (T b ) is under the control of a hierarchy of neuronal structures that must first integrate afferent and central information before activating appropriate physiological and behavioral responses. In mammals, T b is regulated with considerable precision, normally varying by only a few degrees Celsius. This is an important adaptation because most biochemical and physiological processes are temperature dependent. In some conditions, adjustments of T b are beneficial. During infection, an increase in T b (fever) enhances immunologic responses and facilitates recovery and survival of an individual (34). In other conditions (such as during hypoxia), a decrease in T b is also beneficial because lower T b increases survival, primarily through a reduction in metabolic rate (13,38). The preoptic area of anterior hypothalamus (POA-AH) is one of the major neuronal structures involved in the control of T b . In addition to receiving afferent input from peripheral thermoreceptors, the POA-AH responds to central changes in hypothalamic temperature (10).Fever is characterized as a controlled elevation in the thermal set point, which is induced initially by exogenous pyrogens. These exogenous pyrogens induce the synthesis and release of a number of endogenous pyrogens, including IL-1␤, TNF...

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Section: Discussionmentioning

confidence: 99%

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Fraga

Machado²,

Fernandes³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Notably, ET-1 also participates in the febrile response induced by the i.p. injected zymosan (present study) and LPS [16] but not polyinosinic:polycytidylic acid [28], suggesting that ET-1 participates in the febrile response induced by bacteria and fungus but not viruses.…”

Section: Discussionmentioning

confidence: 99%

“…In 1998, Fabrício et al [16] showed that endothelin-1 (ET-1) induced fever when it was injected directly in the brain, and that the ET B receptor antagonist BQ788 reduced LPS-induced fever. These results and those of the following studies [17,18] confirmed that ET-1 is a central mediator of fever.…”

Section: Introductionmentioning

confidence: 99%

Central mediators of the zymosan-induced febrile response

Bastos-Pereira

Fraga

Dreifuss

et al. 2017

Journal of Basic and Clinical Physiology and Pharmacology

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Background: Zymosan is a fungal cell wall protein-carbohydrate complex that is known to activate inflammatory pathways through the Toll-like receptors and is commonly used to induce fever. Nevertheless, the central mediators that are involved in the zymosan-induced febrile response are only partially known. Methods:The present study evaluated the participation of prostaglandins, substance P, endothelin-1 (ET-1), and endogenous opioids (eOPs) in the zymosan-induced febrile response by using inhibitors and antagonists in male Wistar rats. Results: Both nonselective (indomethacin) and selective (celecoxib) cyclooxygenase inhibitors reduced the febrile response induced by an intraperitoneal (i.p.) injection of zymosan. Indomethacin also blocked the increase in the prostaglandin E 2 levels in the cerebrospinal fluid. An intracerebroventricular injection of the neurokinin-1, ET B , and μ-opioid receptor antagonists also reduced the febrile response induced by the i.p. injected zymosan. Moreover, the μ-opioid receptor antagonist CTAP also reduced the febrile response induced by intra-articular injection of zymosan.Conclusions: These results demonstrate that prostaglandins, substance P, ET-1, and eOPs are central mediators of the zymosan-induced febrile response.

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“…These results indicate that while the reduced fever response on fasting is partly attributable to an attenuated central PGE 2 production, the leptin-mediated recovery of fever is not. We also examined the levels of other inflammatory variables that were reported to contribute to the fever response independent of PGE 2 synthesis (3,7,12,37,38). Neither the levels of CSF 15-D-PGJ 2 , MIP-1␤, endothelin-1, NOS-1, NOS-2, nor NOS-3 mRNA was associated with the degree of sustained fever (Table 3).…”

Section: Febrigenic Inflammatory Responses In the Periphery And The Bmentioning

confidence: 99%

Acute starvation alters lipopolysaccharide-induced fever in leptin-dependent and -independent mechanisms in rats

Inoue

Luheshi

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Inoue W, Luheshi GN. Acute starvation alters lipopolysaccharideinduced fever in leptin-dependent and -independent mechanisms in rats. Am J Physiol Regul Integr Comp Physiol 299: R1709 -R1719, 2010. First published October 13, 2010; doi:10.1152/ajpregu.00567.2010.-A decrease in leptin levels with the onset of starvation triggers a myriad of physiological responses including immunosuppression and hypometabolism/hypothermia, both of which can counteract the fever response to pathogens. Here we examined the role of leptin in LPSinduced fever in rats that were fasted for 48 h prior to inflammation with or without leptin replacement (12 g/day). The preinflammation fasting alone caused a progressive hypothermia that was almost completely reversed by leptin replacement. The LPS (100 g/kg)-induced elevation in core body temperature (Tcore) was attenuated in the fasted animals at 2-6 h after the injection, an effect that was not reversed by leptin replacement. Increasing the LPS dose to 1,000 g/kg caused a long-lasting fever that remained unabated for up to 36 h after the injection in the fed rats. This sustained response was strongly attenuated in the fasted rats whose T core started to decrease by 18 h after the injection. Leptin replacement almost completely restored the prolonged fever. The attenuation of the prolonged fever in the fasted animals was accompanied by the diminution of proinflammatory PGE 2 in the cerebrospinal fluid and mRNA of proopiomelanocortin (POMC) in the hypothalamus. Leptin replacement prevented the fasting-induced reduction of POMC but not PGE 2 . Moreover, the leptin-dependent fever maintenance correlated closely with hypothalamic POMC levels (r ϭ 0.77, P Ͻ 0.001). These results suggest that reduced leptin levels during starvation attenuate the sustained fever response by lowering hypothalamic POMC tone but not PGE 2 synthesis. fasting; energy balance; prostaglandin; proopiomelanocortin FEVER IS A COMMON RESPONSE to various types of infection and constitutes an important component of an adaptive strategy for fighting disease (18,29). The development of fever is a finely tuned, complex event that involves both the immune and the central nervous systems through which a series of inflammatory, thermoregulatory, and metabolic processes are regulated (46). The sum of the changes required to mount an effective fever response is an energy-demanding process that can be influenced by the energy status of the host. This was clearly shown by a number of studies reporting that malnutrition prior to the induction of inflammation compromises the fever response in various species of experimental animals (20,21,24,28,30,53,54,60). The suggested explanations for this observation include suppression of inflammatory responses (20,21,53), an alteration of the thermoregulatory response (24, 30), and an attenuation of thermogenic effecter activity (28, 54). However, it remains unclear how the signal relating to the reduced energy status of the host is relayed to the aforementioned fever-related functions and subseq...

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Essential role for endothelin ET_B receptors in fever induced by LPS (E. coli) in rats

Cited by 52 publications

References 55 publications

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Central mediators of the zymosan-induced febrile response

Acute starvation alters lipopolysaccharide-induced fever in leptin-dependent and -independent mechanisms in rats

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Essential role for endothelin ETB receptors in fever induced by LPS (E. coli) in rats

Cited by 52 publications

References 55 publications

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Endogenous opioids: role in prostaglandin-dependent and -independent fever

Central mediators of the zymosan-induced febrile response

Acute starvation alters lipopolysaccharide-induced fever in leptin-dependent and -independent mechanisms in rats

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Essential role for endothelin ET_B receptors in fever induced by LPS (E. coli) in rats