Modulation of lipopolysaccharide-induced tumor necrosis factor-α production by selective α- and β-adrenergic drugs in mice

Elenkov, Ilia J.; Haskó, György; Kovács, Krisztina; Vizi, E.S.

doi:10.1016/0165-5728(95)00080-l

Cited by 166 publications

(85 citation statements)

References 46 publications

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“…64 Plasma IL-1 and TNF-a responses to repeated LPS injections were much smaller than those to acute LPS injection. 64,77 The decreased cytokine production may be due to an alteration in peripheral sympathetic tone, 79,80 but it remains unclear whether repeated LPS injection altered cytokine receptor or neuronal responses at the post-receptor level. A normal glucocorticoid response to endotoxemia seems to be necessary for the development of full tolerance of the HPA axis.…”

Section: Repeated Lps Administrationmentioning

confidence: 99%

“…Peripheral or central administration of these cytokines has been shown to stimulate the HPA axis. 79,80,[125][126][127][128][129] These peripherally produced cytokines, acting through incompletely understood mechanisms, stimulate central stress pathways, 2,15,109,127,[130][131][132][133] activating the HPA axis 14,16 and the end effectors of this axis, cortisol and corticosterone, which restrain the innate and T-cell-specific immune responses. 109,132,133 The pathways from the periphery to brain involved in these responses are largely unknown.…”

Section: Mechanisms For the Effects Of Endotoxin On The Hpa Axismentioning

confidence: 99%

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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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Section: Repeated Lps Administrationmentioning

confidence: 99%

Section: Mechanisms For the Effects Of Endotoxin On The Hpa Axismentioning

confidence: 99%

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

Beishuizen

Thijs

2003

Journal of Endotoxin Research

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“…These findings confirm studies in LPS-treated mice showing: (1) β-AR blockade pretreatment increases; (2) β-AR agonist pretreatment inhibits; and (3) α 2 -AR blockade with the highly selective α 2 -antagonist, CH 38083 reduces plasma TNF-α. Pretreatment with chlorisondamine (a sympathetic ganglionic blocker) prevents the CH 38083-induced effect, suggesting that the α 2 -AR effects are mediated presynaptically [reviewed by 310]. Further, the CH 38083-induced reduction in TNF-α is blocked with addition of the nonselective β-blocker, propranolol, and the β 1 -selective antagonist, atenolol, but not the β 2 -selective antagonist, ICI 118,551, suggesting the effect of the α 2 -antagonist is mediated by β 1 -AR [310].…”

Section: Sympathetic Activation and Endotoxic Shock: Inflammatory Andmentioning

confidence: 99%

“…Pretreatment with chlorisondamine (a sympathetic ganglionic blocker) prevents the CH 38083-induced effect, suggesting that the α 2 -AR effects are mediated presynaptically [reviewed by 310]. Further, the CH 38083-induced reduction in TNF-α is blocked with addition of the nonselective β-blocker, propranolol, and the β 1 -selective antagonist, atenolol, but not the β 2 -selective antagonist, ICI 118,551, suggesting the effect of the α 2 -antagonist is mediated by β 1 -AR [310]. Together, these data suggest a dual role for SNS activation after LPS administration: (1) reduction of TNF-α through β-AR, and (2) In endotoxemic mice, IL-10-induces suppression of TNF-α production and down-regulates an inflammatory response, which reduces their mortality [315].…”

Section: Sympathetic Activation and Endotoxic Shock: Inflammatory Andmentioning

confidence: 99%

Sympathetic modulation of immunity: Relevance to disease

Bellinger

Millar

Perez

et al. 2008

Cellular Immunology

225

185

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Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far as focused on neural-immune modulation in secondary lymphoid organs, and have revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease-or injury-induced 'fight' responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks.

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“…30 min before hemorrhage. This dose of propranolol has previously been shown to produce ␤ -adrenergic blockade in mice as determined by its effects on basal heart rate (38), LPS-induced TNF-␣ release (39), and stress-induced locomotor activity (40).…”

Section: Interventionsmentioning

confidence: 99%

Hemorrhage increases cytokine expression in lung mononuclear cells in mice: involvement of catecholamines in nuclear factor-kappaB regulation and cytokine expression.

et al. 1997

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The expression of proinflammatory and immunoregulatory cytokines rapidly increases in the lungs after hemorrhage, and such alterations contribute to the frequent development of acute inflammatory lung injury in this setting. Blood loss also produces elevations in catecholamine concentrations in the pulmonary and systemic circulation. In the present experiments, we used ␣ -and ␤ -adrenergic receptor blockade to examine in vivo interactions between hemorrhage-induced adrenergic stimulation and pulmonary cytokine expression. Treatment of mice with the ␣ -adrenergic receptor antagonist phentolamine prevented not only the elevation in mRNA levels of IL-1 ␤ , TNF-␣ , and TGF-␤ 1, the increase in IL-1 ␤ protein, but also the activation of nuclear factor (NF)-B and cyclic AMP response element binding protein, which occurred in lung cells of untreated animals during the first hour after hemorrhage. In contrast, treatment before hemorrhage with the ␤ -adrenergic receptor antagonist propranolol was associated with increases in mRNA levels for IL-1 ␤ , TNF-␣ , and TGF-␤ 1, which were greater than those present in untreated hemorrhaged mice, and did not prevent hemorrhage-associated increases in lung IL-1 ␤ protein. Treatment with propranolol prevented hemorrhageinduced phosphorylation of cyclic AMP response element binding protein, but increased hemorrhage-associated activation of NF-B. These results demonstrate that hemorrhage initially increases pulmonary cytokine expression through ␣ -but not ␤ -adrenergic stimulation, and suggest that such ␣ -adrenergic-mediated effects occur through activation of the transcriptional regulatory factor NF-B. ( J. Clin. Invest. 1997. 99:1516-1524.)

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Modulation of lipopolysaccharide-induced tumor necrosis factor-α production by selective α- and β-adrenergic drugs in mice

Cited by 166 publications

References 46 publications

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

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

Sympathetic modulation of immunity: Relevance to disease

Hemorrhage increases cytokine expression in lung mononuclear cells in mice: involvement of catecholamines in nuclear factor-kappaB regulation and cytokine expression.

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