Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 beta depresses the voltage-gated Ca2+ channel currents in acutely dissociated guinea-pig hippocampal CA1 neurons. This depression is observed with pathophysiological concentrations found in the cerebrospinal fluid (> or = 1.0 pg interluekin-1 beta/10 microliters). Interleukin-1 receptor antagonist (in concentrations 25-fold higher than interleukin-1 beta) completely blocked the interleukin-1 beta-induced depression of the Ca2+ channel current. This suggests that interleukin-1 beta action is through a specific interaction with an interleukin-1 membrane receptor site. The application of other cytokines and growth factors (interleukin-6, epidermal growth factor, and basic fibroblast growth factor), or bacterial lipopolysaccharide (endotoxin) had no effect, indicating specificity of action of interleukin-1 beta. The depression of the Ca2+ channel current by interleukin-1 beta was prevented by the extracellular application of pertussis toxin, and by the intracellular application of GDP[beta S], H-7, staurosporine or bisindolylmaleimide. Application of phorbol 12-myristate 13-acetate also depressed the Ca2+ channel current, but this phorbol ester-induced depression was not additive to that induced by interleukin-1 beta. These results suggest mediation of interleukin-1 beta action through a pertussis toxin-sensitive G-protein coupled interleukin-1 receptor associated with the activation of protein kinase C. The depression of the Ca2+ channel current by interleukin-1 beta may be involved in the regulation of neuronal excitability during pathological conditions and in the induction and/or progression of neurodegenerative processes.
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PMID:Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. 813 77

Stressful environmental conditions are a major determinant of immune reactivity. This effect is pronounced in Australian National Antarctic Research Expedition populations exposed to prolonged periods of isolation in the Antarctic. Alterations of T cell function, including depression of cutaneous delayed-type hypersensitivity responses and a peak 48.9% reduction of T cell proliferation to the mitogen phytohaemagglutinin, were documented during a 9-month period of isolation. T cell dysfunction was mediated by changes within the peripheral blood mononuclear cell compartment, including a paradoxical atypical monocytosis associated with altered production of inflammatory cytokines. There was a striking reduction in the production by peripheral blood mononuclear cells of the predominant pro-inflammatory monokine TNF-alpha and changes were also detected in the production of IL-1, IL-2, IL-6, IL-1ra and IL-10. Prolonged Antarctic isolation is also associated with altered latent herpesvirus homeostasis, including increased herpesvirus shedding and expansion of the polyclonal latent Epstein-Barr virus-infected B cell population. These findings have important long-term health implications.
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PMID:Antarctic isolation: immune and viral studies. 924 93

The effect of the pro-inflammatory cytokine, interleukin-1beta on an NMDA receptor-independent form of synaptic plasticity brought about by the application of the K+ channel blocker tetraethylammonium, was examined in the rat dentate gyrus in vitro. Field excitatory postsynaptic potentials (EPSPs) were recorded from the medial perforant path of the dentate gyrus every 20 s. Perfusion of the K+ channel blocker, tetraethylammonium chloride (25 mM) for 10 min and subsequent washout gave rise to robust and long-term potentiation of the field EPSP slope (tetraethylammonium induced long-term potentiation; 125+/-5% of baseline 60 min following tetraethlylammonium-washout; n = 7, P < 0.05) Application of interleukin-1beta (1 ng/ml) for 30 min was found to inhibit the induction, but not the maintenance of the tetraethylammonium induced long-term potentiation (n = 8). Heat denatured interleukin-1beta had no effect on tetraethylammonium induced long-term potentiation (n = 6). The expression of tetraethylammonium induced long-term potentiation was found to be accompanied by an increase in the magnitude of paired pulse depression seen at interstimulus intervals of 20 and 100 ms (controls, 42+/-5% and 13+/-2%; tetraethylammonium, 62+/-5% and 22+/-2% respectively for both intervals; n = 6, P < 0.05). The increase in paired pulse depression at an interstimulus interval of 100 ms was significantly attenuated by pre-treatment of slices with interleukin-1beta. The inhibitory effect of interleukin-1beta on both tetraethylammonium induced long-term potentiation and the tetraethylammonium induced increase in paired pulse depression was antagonised by pre-incubation with the interleukin-1 receptor antagonist. Interleukin-1 receptor antagonist was found to have no effect on tetraethylammonium induced long-term potentiation when applied on its own (n = 5). The p38 mitogen activated protein kinase inhibitor SB203580 (4-(4-fluorophenyl)-2-(4 methylesulfinylphenyl)-5-(4-pyridyl)1H-imidazole) was also found to inhibit the induction of tetraethylammonium induced long-term potentiation (n = 6). These findings suggest a possible role for interleukin-1beta in the modulation of NMDA receptor-independent synaptic plasticity in the rat dentate gyrus.
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PMID:Interleukin-1beta inhibits a tetraethylammonium-induced synaptic potentiation in the rat dentate gyrus in vitro. 1042 60

Severe sepsis and probably most prolonged critical illnesses reflect a paradox of combined increased activation and depression of the immune apparatus. The increased activation of the inflammatory response is evidenced from the increased levels of circulating proinflammatory cytokines in the blood, increased endothelial activation with increased expression of inducible nitric oxide synthase, and increased de novo CD11b expression on circulating immune effector cells, such as PMNs, monocytes and lymphocytes. However, coexisting with this proinflammatory process is a profound anti-inflammatory state characterized by increased circulating levels of anti-inflammatory species that both directly block the binding of proinflammatory stimuli to their cell surface receptors (IL-1ra, soluble TNF receptors) and also induce an anti-inflammatory state on their own (IL-10, TFG-beta). This humoral anti-inflammatory state is mirrored at the cellular levels by decreased monocyte ability to process antigen, characterized by a reduced HLA-DR expression and impaired PMN upregulation in response to clearly proinflammatory stimuli. Accordingly, severe sepsis reflects a combined pro- and anti-inflammatory state. Both the pro- and anti-inflammatory arms have protective and destructive aspects, making their modulation by treatment less predictable than if their actions were purely beneficial or detrimental.
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PMID:Sepsis: a pro- and anti-inflammatory disequilibrium syndrome. 1139 3

The relationship between immune activation and the development of early depressive symptoms were studied in 33 cancer patients undergoing cytokine therapy. Patients were treated either with subcutaneous IL-2 administered alone (n=13) or in association with IFN-alpha (n=5), or with IFN-alpha alone administered subcutaneously at low doses (n=5) or intravenously at high doses (n=10). The intensity of depressive symptoms was assessed during a clinical interview carried out before the start of cytokine therapy and five days later using the Montgomery and Asberg Depression Rating Scale (MADRS). On the same days, blood samples were collected for each patient to measure serum concentrations of cytokines (IL-6, IL-10, IL-1ra) and cytokine-receptors (sIL-2R, LIF-R). Results showed that patients treated with IL-2 or IL-2+IFN-alpha displayed concomitant mood symptoms and increased serum cytokine levels during treatment. In these patients, the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint. IL-10 is an anti-inflammatory cytokine that is produced in response to the production of pro-inflammatory cytokines, and thereby reflects an inflammatory response. These results support the hypothesis of close relationship between depressive symptoms and the activation of the cytokine network.
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PMID:Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy. 1158 80

The effects of the pro-inflammatory cytokine interleukin-18 (IL-18) were investigated on both normal and isolated N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory post synaptic potentials (fEPSP) and on the induction of long-term potentiation (LTP) in the rat dentate gyrus in vitro. Bath perfusion with IL-18 (100 ng/ml) for 20 min prior to high-frequency stimulation had no significant effect on baseline synaptic transmission or paired pulse depression, but did impair the induction of LTP (115.7+/-8.8% versus 150.8+/-8.1% in vehicle control slices, n=6, P<0.05 at 60 min). Further analysis demonstrated that IL-18 significantly depressed the amplitude of pharmacologically isolated NMDA receptor-mediated fEPSP (NMDA-fEPSP; 77.4+/-4.3% of baseline compared to controls at 1 h; P<0.05, n=7), an effect that may underlie the impairment of LTP by IL-18. This action of IL-18 on LTP and NMDA-fEPSPs was attenuated in full by pretreatment of slices with exogenously applied IL-1 receptor antagonist (IL-1ra, 100 ng/ml), the naturally occurring antagonist of IL-1 type 1 receptors. This ability of IL-1ra to block the inhibitory effects of IL-18 is likely to be receptor-specific as no reversal of the tumour necrosis factor-alpha-induced inhibition of LTP was seen with IL-1ra administration (110.7+/-5.4% versus tumour necrosis factor-alpha-treated slices; 107.4+/-8.7%, P=0.6, n=6). These are the first experiments providing evidence of a direct neuromodulatory role for IL-18 in synaptic plasticity.
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PMID:The pro-inflammatory cytokine interleukin-18 impairs long-term potentiation and NMDA receptor-mediated transmission in the rat hippocampus in vitro. 1173 33

EAE is associated with sickness behavior symptoms that are temporally correlated with inflammatory processes. To further elucidate the role of inflammatory mediators in the behavioral syndrome, EAE mice were injected daily with anti-inflammatory drugs, beginning at disease onset. Dexamethasone or interleukin-1 (IL-1) receptor antagonist or the prostaglandins synthesis inhibitor indomethacin attenuated the behavioral symptoms. Administration of the tumor necrosis-factor alpha (TNF-alpha) synthesis inhibitor pentoxifylline or targeted deletion of the type I TNF receptor had no behavioral effects whereas administration of pentoxifylline in IL-1ra-treated mice further reversed the behavioral depression. These findings demonstrate the critical involvement of pro-inflammatory cytokines and prostaglandins in the EAE-associated behavioral syndrome, and may have implications for understanding and treating the neuropsychiatric disturbances in multiple sclerosis (MS) patients.
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PMID:The EAE-associated behavioral syndrome: II. Modulation by anti-inflammatory treatments. 1266 53

In this study the effect of IL-1 beta on [(3)H]purine release from rat hippocampal slices was explored. IL-1 beta (3 x 10(-18)-3 x 10(-14) M) concentration-dependently elevated the basal [(3)H]purine efflux, and this effect was reversed by the selective IL-1RI receptor antagonist IL-1ra (10(-12) M). HPLC analysis revealed that the amount of [(3)H]ATP and [(3)H]adenosine significantly increased in the effluent in response to IL-1 beta. The sodium channel inhibitor tetrodotoxin, the NMDA and non-NMDA receptor antagonists d(-)-2-amino-5-phosphonopentanoic acid (AP-5) plus 6-cyano-7-nitroquinoxaline-2,3-dione-disodium (CNQX) almost completely abolished IL-1 beta-evoked [(3)H]purine release. The effect of IL-1 beta on [(3)H]purine efflux was also prevented by the p38 MAP kinase inhibitor SB 203580, by the nucleoside transport inhibitor nitrobenzyl-thioinosine (NBTI) and by low temperature (4 degrees C). In summary IL-1 beta triggers a transporter mediated [(3)H]purine efflux in the hippocampus which is conveyed by glutamate receptor activation and the p38 MAP kinase pathway, and could serve as a mediator of IL-1 beta-induced synaptic depression.
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PMID:Potent effect of interleukin-1 beta to evoke ATP and adenosine release from rat hippocampal slices. 1514 1

The association between inflammation and neuropsychiatric symptoms in old age is generally accepted but poorly understood. The purpose of this study was to examine whether inflammation precedes depressive symptoms and cognitive decline in old age, and to identify specific inflammatory pathways herein. We measured serum C-reactive protein (CRP) and lipopolysaccharide-induced production of Interleukin (IL)-1beta, IL-6, Tumor Necrosis Factor (TNF)-alpha, IL-1 receptor antagonist (ra), and IL-10 levels in 85-year-old participants free from neuropsychiatric symptoms at baseline (n=267). Participants were prospectively followed for depressive symptoms (Geriatric Depression Scale) and cognitive functioning (Mini Mental State Examination) from 85 to 90 years. Higher baseline CRP levels preceded accelerated increase in depressive symptoms (p<0.001). A higher production capacity of the pro-inflammatory cytokine IL-1beta preceded a greater increase of depressive symptoms (p=0.06), whereas that of its natural antagonist IL-1ra preceded a smaller increase of depressive symptoms (p=0.003). There was no relation of CRP, IL-1beta, and IL-1ra with cognitive decline. Our findings show that in old age inflammatory processes contribute to the development of depressive symptoms but not cognitive decline. A high innate IL-1ra to IL-1beta production capacity reflects a better ability to neutralize inflammation and may therefore protect against depressive symptoms.
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PMID:Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. 1735 Jul 81

Although receptors for the pro-inflammatory cytokine interleukin-1 have long been known to be expressed in the brain, their role in fever and behavioural depression observed during the acute phase response (APR) to tissue infection remains unclear. This may in part be due to the fact that interleukin-1 in the brain is bioactive only several hours after peripheral administration of bacterial lipopolysaccharide (LPS). To study the role of cerebral interleukin-1 action in temperature and behavioural changes, and activation of brain structures during the APR, interleukin-1 receptor antagonist (IL-1ra; 100 microg) was infused into the lateral brain ventricle 4 h after intraperitoneal (i.p.) LPS injection (250 microg/kg) in rats. I.p. LPS administration induced interleukin-1beta (IL-1beta) production in systemic circulation as well as in brain circumventricular organs and the choroid plexus. Intracerebroventricular (i.c.v.) infusion of IL-1ra 4 h after i.p. LPS injection attenuated the reduction in social interaction, a cardinal sign of behavioural depression during sickness, and c-Fos expression in the amygdala and bed nucleus of the stria terminalis. However, LPS-induced fever, rises in plasma corticosterone, body weight loss and c-Fos expression in the hypothalamus and caudal brainstem were not altered by i.c.v. infusion of IL-1ra. These findings, together with our previous observations showing that i.c.v. infused IL-1ra diffuses throughout perivascular spaces, where macrophages express interleukin-1 receptors, can be interpreted to suggest that circulating or locally produced brain IL-1beta acts on these cells to bring about behavioural depression and activation of limbic structures during the APR after peripheral LPS administration.
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PMID:Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide. 1908 75


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