Benzodiazepine anethesia in humans modulates the interleukin-1β, tumor necrosis factor-α and interleukin-6 responses of blood monocytes

Taupin, Véronique; Jayais, P.; Descamps‐Latscha, Béatrice; Jb, Cazalaà; Barrier, G.; Bach, Jean‐François; Zavala, Flora

doi:10.1016/0165-5728(91)90157-3

Cited by 41 publications

(23 citation statements)

References 20 publications

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“…Moreover, high levels of TNFalpha have been associated with symptoms of anxiety in humans under conditions of psychological stress 52 or following administration of LPS. 53 Interestingly, benzodiazepines have been shown to inhibit LPSinduced production of TNF-alpha from human microglial cells 54 and monocytes 55 as well as murine macrophages. 56 These findings suggest that inhibition of TNF-alpha production (or other proinflammatory cytokines), centrally or peripherally, could contribute to the mechanism of action of these anxiolytic agents.…”

Section: Discussionmentioning

confidence: 99%

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Silverman

MacDougall

et al. 2006

Mol Psychiatry

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Endogenous glucocorticoids restrain proinflammatory cytokine responses to immune challenges such as viral infection. In addition, proinflammatory cytokines induce behavioral alterations including changes in locomotor/exploratory activity. Accordingly, we examined proinflammatory cytokines and open-field behavior in virally infected mice rendered glucocorticoid deficient by adrenalectomy (ADX). Mice were infected with murine cytomegalovirus (MCMV), and open-field behavior (36 h post-infection) and plasma concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 (42 h post-infection) were assessed. Compared to sham-ADX-MCMV-infected animals, ADX-MCMV-infected mice exhibited significant reductions in total distance moved, number of center entries, and time spent in center. These behavioral alterations were accompanied by significantly higher plasma concentrations of TNF-alpha and IL-6, both of which were correlated with degree of behavioral change. To examine the role of TNF-alpha in these behavioral alterations, open-field behavior was compared in wild-type (WT) and TNF-R1-knockout (KO), ADX-MCMV-infected mice. TNF-R1-KO mice exhibited significantly attenuated decreases in number of rearings, number of center entries and time spent in center, but not distance moved, which correlated with plasma IL-6. Given the potential role of brain cytokines in these findings, mRNA expression of TNF-alpha, IL-1 and IL-6 was assessed in various brain regions. Although MCMV induced increases in proinflammatory cytokine mRNA throughout the brain (especially in ADX animals), no remarkable differences were found between WT and TNF-R1-KO mice. These results demonstrate that endogenous glucocorticoids restrain proinflammatory cytokine responses to viral infection and their impact on locomotor/exploratory activity. Moreover, TNF-alpha appears to mediate cytokine-induced changes in open-field behaviors, especially those believed to reflect anxiety.

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Section: Discussionmentioning

confidence: 99%

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Silverman

MacDougall

et al. 2006

Mol Psychiatry

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“…The PBRs are first discovered in peripheral organs and later in the CNS, where they are associated with glial cells [3]. PBRs are expressed in immune cells abundantly and there are reports that benzodiazepines could modulate immune responses through interaction with PBRs in immune cells [4][5][6][7][8]. However, most of the studies are focused on monocytes and macrophages.…”

Section: Introductionmentioning

confidence: 99%

Suppressive effect of diazepam on IFN-γ production by human T cells

Wei

Meng

et al. 2010

International Immunopharmacology

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“…These receptors have been located in peripheral tissue such as monocytes (Canat et al 1993) and in brain in human (Banati et al 1997) and murine (Park et al 1996) microglia. Agonists of the PBR have been reported to suppress immune responses through the modulation of monocyte proliferation and secretion of a variety of cytokines including IL-1b, TNF-a, and IL-6 (Zavala et al 1990;Taupin et al 1991). Certain benzodiazepine derivatives such as the isoquinolinecarboxamide compound PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide] act as specific ligands of the PBR (Kinnally et al 1993;Hirsch et al 1998) and act to modulate immune responses in vitro and in vivo (Taupin et al 1991;Vowinckel et al 1997;Torres et al 1999;Klegeris et al 2000).…”

mentioning

confidence: 99%

Inhibition of lipopolysaccharide‐induced cyclooxygenase‐2, tumor necrosis factor‐α and [Ca²⁺]_i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195

Choi¹,

Khoo²,

Ryu³

et al. 2002

Journal of Neurochemistry

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The anti-inflammatory actions of the mitochondrial peripheral benzodiazepine receptor (PBR) agonist PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide] were investigated in human microglia. Application of the microglial inflammatory stimulus lipopolysaccharide (LPS, at 100 ng/mL for 3 h), induced enhancement of the expressions of the inducible enzyme, cyclooxygenase-2 (COX-2) and the pro-inflammatory cytokine, tumor necrosis factor-a (TNF-a). PK11195 (at 50 lM) significantly inhibited the LPSinduced up-regulation of both inflammatory factors; at a lower concentration of PK11195 (2 lM) expression of TNF-a, but not COX-2, was reduced. Production of both factors, using immunocytochemistry for COX-2 and ELISA for TNF-a, was markedly reduced with 50 lM of PK11195 added to LPS solution. Acute application of LPS induced a transient increase in intracellular Ca 2+ [Ca 2+ ] i exhibiting both a slow development and recovery in kinetic behavior. This increase in [Ca 2+ ] i consisted primarily of a Ca 2+ influx component accompanied by a smaller mobilization from intracellular Ca 2+ stores. In the presence of PK11195, the amplitude of the [Ca 2+ ] i response induced by LPS was reduced by 54%. Another mitochondrial agent cyclosporin A (CsA), which also acts at the permeability transition pore (PTP) of mitochondrial membrane but at a site different from the PBR, was ineffective in reducing either the LPS-induced expression of COX-2 and TNF-a or the endotoxin increase in [Ca 2+ ] i . These results indicate that the mitochondrial effector PK11195 is a specific and effective agent for inhibiting LPS-induced microglial expressions of COX-2 and TNF-a and that modulation of Ca 2+ -mediated signaling pathways could be involved in the anti-inflammatory actions. Keywords: cyclooxygenase-2, human microglia, intracellular calcium, lipopolysaccharide, mitochondrial effector, PK11195, tumor necrosis factor-a. Microglia are resident cells of the CNS that serve a functional role as scavenger cells similar to that of peripheral macrophages. These cells have been implicated as key mediators of inflammation in the CNS, during which microglia proliferate and contribute to the inflammatory process by phagocytosis and secretion of cytokines, eicosanoids and other agents (McGeer and McGeer 1995). Although inflammation of the CNS is intended as a homeostatic means to contain damage to neural tissue, such damage may occur from the inflammatory process itself (McGeer and McGeer 1995;Rogers and Griffin 1998). In this case microglial responses to inflammatory stimuli in the brain may actually exacerbate, rather than inhibit, neuronal damage. Abbreviations used: [Ca 2+ ] i , intracellular calcium concentration; COX-2, cyclooxygenase-2; CsA, cyclosporin A; DAPI, 4,6-diaminodino-2-phenylindole; DMEM, Dulbecco's modified Eagle's medium; ER, endoplasmic reticulum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LPS, lipopolysaccharide; PBS, phosphate-buffered saline; PBR, peripheral benzodiazepine receptor; PK11195...

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Benzodiazepine anethesia in humans modulates the interleukin-1β, tumor necrosis factor-α and interleukin-6 responses of blood monocytes

Cited by 41 publications

References 20 publications

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Suppressive effect of diazepam on IFN-γ production by human T cells

Inhibition of lipopolysaccharide‐induced cyclooxygenase‐2, tumor necrosis factor‐α and [Ca²⁺]_i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195

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Benzodiazepine anethesia in humans modulates the interleukin-1β, tumor necrosis factor-α and interleukin-6 responses of blood monocytes

Cited by 41 publications

References 20 publications

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Suppressive effect of diazepam on IFN-γ production by human T cells

Inhibition of lipopolysaccharide‐induced cyclooxygenase‐2, tumor necrosis factor‐α and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195

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Inhibition of lipopolysaccharide‐induced cyclooxygenase‐2, tumor necrosis factor‐α and [Ca²⁺]_i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195