Glucocorticoid‐dependent and ‐independent mechanisms involved in lipopolysaccharide tolerance

Evans, Glenn F.; Zuckerman, Steven H.

doi:10.1002/eji.1830210902

Cited by 83 publications

(66 citation statements)

References 43 publications

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“…The role of endogenous glucocorticoids in the regulation of LPS effects is supported by the fact that the high sensitivity of adrenalectomized animals to LPS shock can be reversed by administration of DEX [10]. Moreover, the progesterone and glucocorticoid inhibitor, RU-486, deactivates the state of tolerance to LPS [34], suggesting that the regulation of glucocorticoids and/or GcR is a key factor [10,28] in mechanisms where LPS is involved.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the progesterone and glucocorticoid inhibitor, RU-486, deactivates the state of tolerance to LPS [34], suggesting that the regulation of glucocorticoids and/or GcR is a key factor [10,28] in mechanisms where LPS is involved.…”

Section: Discussionmentioning

confidence: 99%

“…), were as follows: IL-1b at 12 ng/mouse: 13 ± 6; IL-1b at 25 ng/mouse: 17 ± 4; IL-1b at 50 ng: 25 ± 3*; IL-1b at 100 ng, 61 ± 6** versus saline: 15 ± 1, *P < 0·001; **P < 0·0001, n = 6. Considering the fact that glucocorticoids from endogenous sources regulate LPS effects [10], we speculated that the secretion of glucocorticoids by IL-1b could also be involved in the induction of endotoxin tolerance. We found that 2·5 mg/kg dexamethasone (DEX) injected i.p.…”

Section: Low Doses Of Il-1b Induce Tolerance To Lps In Vivo In the Prmentioning

confidence: 99%

“…The latter can be induced by minute amounts of LPS, which render the host temporarily refractory to subsequent lethal doses of LPS challenge, as well as to other inflammatory stimuli [6]. This phenomenon, known as LPS or endotoxin tolerance, shows a reduced capacity of monocytes/macrophages to synthesize pro-inflammatory cytokines upon re-exposure to LPS [3,[9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-1β inducesin vivotolerance to lipopolysaccharide in mice

Alves-Rosa

Vulcano

Beigier-Bompadre

et al. 2002

Clinical and Experimental Immunology

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SUMMARYEndotoxin or lipopolysaccharide (LPS) tolerance may be partially due to the secretion of potent antiinflammatory cytokines following severe Gram-negative infections, or by low doses of LPS. In this work, we describe the effects of interleukin-1b (IL-1b) and tumour necrosis factor alpha (TNF-a), two early cytokines secreted after LPS exposure, in the induction of LPS tolerance. Our results demonstrate that mice treated with three daily doses of 100 ng of IL-1b were tolerant to LPS-induced shock. However, TNF-a was unable to induce an LPS refractory state. Given the fact that 100 ng of IL-1b increase the plasma levels of glucocorticoids, we evaluated whether a daily injection of dexamethasone (DEX) alone was able to reproduce the LPS-like tolerant state. However, no signs of LPS refractoriness were detected, except when DEX was administered concomitantly with a dose of IL-1b that does not induce corticosterone secretion (12 ng/mouse). This dose was found to induce in vitro up-regulation of the glucocorticoid receptors (GcR) of peritoneal macrophages following 24 h of treatment. In addition, we demonstrate that IL-1b is capable of inducing the down-regulation of Toll-like receptor 4 (TLR4), a crucial molecule in the signal transduction of LPS. Taken together, our results indicate that IL-1b can generate tolerance to LPS in vivo, and suggest that the regulation of mechanisms of the downregulation of TLR4, as well as those involved in the expression of GcR and/or in the secretion of glucocorticoids, would be crucial for these effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Low Doses Of Il-1b Induce Tolerance To Lps In Vivo In the Prmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interleukin-1β inducesin vivotolerance to lipopolysaccharide in mice

Alves-Rosa

Vulcano

Beigier-Bompadre

et al. 2002

Clinical and Experimental Immunology

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“…In male mice, the occurrence of a tolerance in HPA axis response has been observed after chronic LPS or TNF-a but not after IL-1 administration. 191 The tolerance of the immune system for the release of TNF-a after multiple LPS injections seems to be mediated by the release of endogenous glucocorticoids as a consequence of the immune challenge, 189 thus indicating a negative feedback mechanism for glucocorticoids on the immune system. 142 Hadid et al showed that TNF-a plays an important role in stimulating the HPA axis after a single, but not after repeated, endotoxin injections and that an impairment in the HPA axis response to both immunoneuroendocrine (LPS) and neuro-endocrine (insulin) is present after repeated LPS administration.…”

Section: 161177178mentioning

confidence: 99%

Review: Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis

Beishuizen

Thijs

2003

Journal of Endotoxin Research

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Endotoxin is considered to be a systemic (immunological) stressor eliciting a prolonged activation of the hypothalamo-pituitary-adrenal (HPA) axis. The HPA-axis response after an endotoxin challenge is mainly due to released cytokines (IL-1, IL-6 and TNF-a) from stimulated peripheral immune cells, which in turn stimulate different levels of the HPA axis. Controversy exists regarding the main locus of action of endotoxin on glucocorticoid secretion, since the effect of endotoxin on this neuro-endocrine axis has been observed in intact animals and after ablation of the hypothalamus; however, a lack of LPS effect has been described at both pituitary and adrenocortical levels. The resulting increase in adrenal glucocorticoids has well-documented inhibitory effects on the inflammatory process and on inflammatory cytokine release. Therefore, immune activation of the adrenal gland by endotoxin is thought to occur by cytokine stimulation of corticosteroidreleasing hormone (CRH) production in the median eminence of the hypothalamus, which, in turn stimulates the secretion of ACTH from the pituitary. Acute administration of endotoxin stimulates ACTH and cortisol secretion and the release of CRH and vasopressin (AVP) in the hypophysial portal blood. During repeated endotoxemia, tolerance of both immune and HPA function develops, with a crucial role for glucocorticoids in the modulation of the HPA axis. A single exposure to a high dose of LPS can induce a long-lasting state of tolerance to a second exposure of LPS, affecting the response of plasma TNF-a and HPA hormones. Although there are gender differences in the HPA response to endotoxin and IL-1, these responses are enhanced by castration and attenuated by androgen and estrogen replacement. Estrogens attenuate the endotoxin-induced stimulation of IL-6, TNF-a and IL-1ra release and subsequent activation in postmenopausal women. There appears to be a temporal and functional relation between the HPA-axis response to endotoxin and nitric oxide formation in the neuro-endocrine hypothalamus, suggesting a stimulatory role for nitric oxide in modulating the HPA response to immune challenges. demonstrate higher plasma levels of IL-1 and TNF-a. Elevation of plasma glucocorticoids results in suppression of cytokines such as IL-1, IL-6, and TNF-a and in up-regulation of other cytokines, such as IL-4 and IL-10, and cytokine receptors. Thus, by regulation of cytokine production and action, the HPA axis contributes to modulation of the response to inflammation/infection. In addition, the role of HPA activation has been suggested to be a negative feedback system provided by the immunosuppressive activity of glucocorticoids, limiting inflammatory responses and preventing the immune system from over-reacting and causing tissue damage or autoimmunity.As early as 1957, Wexler et al. suggested that LPS could induce ACTH release since they found a depletion of ascorbic acid and cholesterol in the adrenal glands. 10 Moreover, LPS was not able to cause these changes in hypophysectomized rats. ...

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Modulation of peripheral blood mononuclear cell activation status duringsalmonella-triggered reactive arthritis

Kirveskari¹,

He²,

Holmström

et al. 1999

Arthritis & Rheumatism

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High levels of expression of some activation and adhesion molecules and elevated levels of mRNA for certain cytokines that are predominantly produced by monocytes were found in PBMC from patients with acute Salmonella-triggered ReA, which suggests that these cells are activated. On the other hand, complete down-regulation of CD14 and a marked decrease in the cytokine production capacity during amelioration of the disease suggest that suppression of PBMC activity might be involved in recovery from ReA.

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Glucocorticoid‐dependent and ‐independent mechanisms involved in lipopolysaccharide tolerance

Cited by 83 publications

References 43 publications

Interleukin-1β inducesin vivotolerance to lipopolysaccharide in mice

Interleukin-1β inducesin vivotolerance to lipopolysaccharide in mice

Review: Endotoxin and the hypothalamo-pituitary-adrenal (HPA) axis

Modulation of peripheral blood mononuclear cell activation status duringsalmonella-triggered reactive arthritis

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