Role of Several Mediators of Inflammation on the Mouse Hypothalamo-Pituitary-Adrenal Axis Response during Acute Endotoxemia

Hadid, Rafi; Spinedi, Eduardo; Chautard, Thierry; Giacomini, Marco; Gaillard, Rolf C.

doi:10.1159/000026393

Cited by 37 publications

(25 citation statements)

References 33 publications

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“…These findings suggest that EtOH impairs IL-6 signaling at cytokine generation and receptor expression levels, which may have important implications, considering that this cytokine plays an important role in inflammation and activation of hypothalamic-pituitary-adrenal (HPA) axis (Hadid et al, 1999;Kamimura et al, 2003;Gabay, 2006).…”

Section: Discussionmentioning

confidence: 98%

Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance

El-Guindy¹,

Villiers²,

Doherty³

2007

Alcohol

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Previous studies have shown that alcohol (EtOH) intoxication impairs lung immunity by affecting cytokines pivotal to the inflammatory process. The objective of this study was to test the hypothesis that acute alcohol intoxication impairs lung innate immunity by down-regulating the expression of pro-inflammatory mediators while simultaneously up-regulating anti-inflammatory mediators. EtOH was administered to the mice 0.5 h prior to an intra-tracheal injection of E. coli lipopolysaccharide (LPS). The animals were killed either 4 or 24 h after LPS to recover plasma, lungs and bronchoalveolar lavage fluid. Lung inflammatory cytokines TNF-α, IL-1β, IL-6, MIF, IL-10, TGF-β and receptors for TNF-α, IL-1β, IL-6 and TGF-β as well as gp130 and corticosterone levels were evaluated at mRNA and protein level. While the mRNA expression and the soluble TNF-Rp55 levels were significantly up-regulated by EtOH, LPS-induced TNF-α activity, TNF-Rp55 mRNA expression and soluble TNF-Rp55 levels were significantly suppressed. The LPS-induced expression of IL-1β, IL-6, MIF, gp130, and receptors IL-1RI, IL-1RII and IL-6Rα were also significantly impaired by EtOH. EtOH increased significantly basal IL-10 activity at 3 h, which continued to remain elevated even at 24 h. The EtOH effect on IL-10 activity persisted even in LPS-challenged mice. EtOH and LPS augmented lung corticosterone levels independently of each other. EtOH suppressed up-regulation of TGF-β1 mRNA expression by LPS and blocked completely LPSinduced TGF-β1 secretion. In conclusion, the data suggest that the suppression of acute lung inflammation by EtOH intoxication is largely due to impairment by EtOH of pro-inflammatory cytokine signaling at the levels of cytokine expression and secretion as well as receptor expression and soluble receptor activity. The augmentation by EtOH of anti-inflammatory mediators' secretion most likely shifts the cytokine balance in the anti-inflammatory direction.

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Section: Discussionmentioning

confidence: 98%

Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance

El-Guindy¹,

Villiers²,

Doherty³

2007

Alcohol

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“…Both LPS and inflammatory cytokines stimulate the hypothalamic-pituitary-adrenal axis, resulting in increased GC release (Takemura et al, 1997;Dunn et al, 1999;Hadid et al, 1999). This is thought to be a means to rein in the maximal extent of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Chronic Unpredictable Stress Exacerbates Lipopolysaccharide-Induced Activation of Nuclear Factor-κB in the Frontal Cortex and Hippocampus via Glucocorticoid Secretion

Munhoz¹,

Lepsch²,

Kawamoto³

et al. 2006

J. Neurosci.

252

232

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Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. The transcription factor nuclear factor-B (NF-B), which is inhibited by GCs, regulates numerous genes central to inflammation. In this study, the effects of stress, GCs, and NMDA receptors on lipopolysaccharide (

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“…Blockade of TNF, and to a lesser degree of IL-1, leads to reduction of the HPA response to endotoxin, whereas anti-IL-6 had no effect. Adapted from Hadid et al 170 In a recent study, the peak response and temporal release patterns of immune and endocrine parameters in human volunteers after different dosages of LPS were studied. 48 It was found that LPS increased the levels of TNF-a and IL-6 as well as the levels of ACTH and cortisol.…”

Section: 161177178mentioning

confidence: 99%

“…170 Using specific blockers of several cytokines, they found that TNF-a, and to a lesser extent IL-1, are the most relevant cytokines involved in HPA axis response to acute endotoxin administration (Fig. 3).…”

mentioning

confidence: 98%

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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Role of Several Mediators of Inflammation on the Mouse Hypothalamo-Pituitary-Adrenal Axis Response during Acute Endotoxemia

Cited by 37 publications

References 33 publications

Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance

Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance

Chronic Unpredictable Stress Exacerbates Lipopolysaccharide-Induced Activation of Nuclear Factor-κB in the Frontal Cortex and Hippocampus via Glucocorticoid Secretion

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

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