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)

This clinical study compared the expression of circulating proinflammatory (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6) and anti-inflammatory (interleukin-10) cytokines and soluble apoptosis mediators (Fas/Fas ligand) between patients with stable chronic heart failure and depressive symptoms (as estimated by the Zung Self-Rating Depression Scale) (n = 15) and those without these symptoms (n = 20). Patients with depressive symptoms exhibited significantly higher levels of TNF-alpha and soluble Fas ligand, as well as significantly lower levels of interleukin-10, than patients without emotional distress. A disregulated cytokine network and activated apoptosis signaling molecules may be actively implicated in the pathophysiology of chronic emotional distress and depressive symptoms in patients with heart failure.
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PMID:Comparison of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure with versus without symptoms of depression. 1554 Dec 60

TNF-alpha has been shown to be involved in cardiac dysfunction during ischemia/reperfusion injury; however, no information regarding the status of TNF-alpha production in myocardial injury due to intracellular Ca2+-overload is available in the literature. The intracellular Ca2+-overload was induced in the isolated rat hearts subjected to 5 min Ca2+-depletion and 30 min Ca2+-repletion (Ca2+-paradox). The Ca2+-paradox hearts exhibited a dramatic depression in left ventricular developed pressure, a marked elevation in left ventricular end diastolic pressure, and more than a 4-fold increase in TNF-alpha content. The ratio of cytosolic to homogenate nuclear factor-kappaB (NFkappaB) was decreased whereas the ratio of phospho-NFkappaB to total NFkappaB was increased in the Ca2+-paradox hearts. All these changes due to Ca2+-paradox were significantly attenuated upon treating the hearts with 100 microM pentoxifylline. These results suggest that activation of NFkappaB and increased production of TNF-alpha may play an important role in cardiac injury due to intracellular Ca2+-overload.
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PMID:TNF-alpha as a potential mediator of cardiac dysfunction due to intracellular Ca2+-overload. 1562 29

We investigated the anti-inflammatory role of conjugated linoleic acid (CLA) in inflammation-challenged weaned pigs and in in vitro cultured peripheral blood mononuclear cells (PBMCs). To test the hypothesis that inflammation responses can be attenuated by dietary CLA supplementation, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS). After 14 d of dietary supplementation with either 2% soybean oil or 2% CLA, half of the pigs in each diet group were challenged with LPS. Dietary CLA alleviated growth depression and prevented the elevations in production and mRNA expression of proinflammatory cytokines [i.e., interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha] induced by the LPS challenge. CLA enhanced the expression of interleukin-10 (IL-10) and peroxisome proliferator-activated receptor-gamma (PPARgamma) in spleen and thymus. To further elucidate the inhibitory effects and the mechanism of action of CLA on cytokine profiles (i.e., IL-1beta, IL-6, and TNF-alpha), PBMCs were isolated from weaned pigs and cultured in media containing cis-9, trans-11 (9c,11t) CLA and trans-10, cis-12 (10t,12c) CLA. Each CLA isomer suppressed the production and expression of IL-1beta, IL-6, and TNF-alpha, and enhanced PPARgamma activation and gene expression in cultured PBMCs. At the molecular level, the inhibitory actions of CLA on IL-1beta, IL-6, and TNF-alpha are attributable mainly to 10t,12c-CLA and the anti-inflammatory properties of CLA are mediated, at least in part, through a PPARgamma-dependent mechanism.
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PMID:Conjugated linoleic acid attenuates the production and gene expression of proinflammatory cytokines in weaned pigs challenged with lipopolysaccharide. 1567 Dec 20

Sex hormones are important modifiers of the acute inflammatory response to injury, an important aspect of myocardial depression and apoptosis following ischemia or endotoxemia. Hemorrhage, trauma, ischemia/reperfusion, burn and sepsis each lead to cardiac dysfunction. Gender has been shown to influence the inflammatory response as well as outcomes following acute injury. The mechanisms by which sex affects the inflammatory response and the outcome to acute injury are being actively investigated. It is now recognized that myocardial inflammation plays a crucial role in I/R-induced myocardial dysfunction. Inflammatory mediators, such as TNF-alpha are produced by cardiomyocytes and contribute to myocardial functional depression and apoptosis. Gender differences in the inflammatory response following burn injury have been demonstrated. However, gender differences in the setting of acute I/R-induced inflammation are unclear. In addition, a critical component of the signal transduction pathway leading to myocardial inflammation is the activation of p38 mitogen-activated protein kinase (MAPK). In other systems, it appears that gender differences exist in the p38 MAPK signaling pathway. The inflammatory response, including the p38 MAPK signaling cascade and expression of proinflammatory cytokines such as TNF-alpha and IL-1beta, may precipitate cardiomyocyte apoptosis following I/R injury. Apoptosis may be an essential component in the pathogenesis of heart failure, and there is evidence that myocyte apoptosis in the failing human heart is markedly lower in women than in men. The prevention of cell death attenuates I/R-induced injury on myocardial anatomy and performance. This review will: 1) examine evidence for gender differences in the outcome to acute injury; 2) explain the myocardial inflammatory response to acute injury; and 3) elucidate the various mechanisms by which gender and sex hormones affect the myocardial response to acute injury.
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PMID:Intracellular signaling mechanisms of sex hormones in acute myocardial inflammation and injury. 1576 71

Recombinant human interferon-alpha (IFN-alpha) induces depression, and neuroendocrine and neuroimmune activation, in a significant number of patients undergoing treatment for viral illnesses (e.g., hepatitis C), yet these effects have not been consistently reproduced in rodents. As such, we sought to determine the effects of acute or chronic IFN-alpha treatment on basic reward and immobility in the forced swim test (FST), neuroendocrine and neuroimmune activation, and monoamine turnover in brain. In the first experiment, male Wistar rats (N = 7/group) treated with human recombinant IFN-alpha (100,000 IU/kg, i.p.), as compared to saline, did not exhibit alterations to rate of sucrose pellet self-administration or total reinforcers obtained, corticosterone release, plasma IL-6 release, IL-1beta or IL-6 mRNA expression in hippocampus, or monoamine turnover in prefrontal cortex, striatum, nucleus accumbens, or amygdala. However, acute IFN-alpha decreased body weight and produced a trend toward reduced food consumption in the home cage 2 h after injection. In the second experiment, Wistar rats (N=4/group) were subjected to a chronic treatment regimen of saline or IFN-alpha (100,000 IU/kg, i.p.) once daily for 14 consecutive days. The data reveal that animals exposed to chronic IFN-alpha exhibited similar amounts of time immobile and similar latencies to primary immobility in the FST as compared to saline-treated controls. Chronic IFN-alpha did not induce corticosterone release, plasma TNF-alpha, or IL-6 release. Tissue monoamine analysis revealed that chronic IFN-alpha reduced DA levels in prefrontal cortex, and decreased 5-HT levels and increased 5-HT turnover in amygdala. In the third experiment, Wistar rats (N = 4/group) were exposed to either acute or chronic pegylated IFN-alpha (pegIFN-alpha: 3.25, 10 or 75 mg/kg, i.p.) at one of several time points from 1 h to 23 days. The data reveal that neither acute nor chronic pegIFN-alpha induced corticosterone release. Overall, the current report demonstrates that neither acute nor chronic IFN-alpha induced depressive-like behavior and neither IFN-alpha nor peg-IFN-alpha was capable of inducing neuroendocrine or neuroimmune activation. Despite the neurochemical alterations observed in the chronic treatment regimen, the data indicate that recombinant human IFN-alpha does not produce a robust model of depressive-like behavior in rodents.
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PMID:Recombinant human interferon-alpha does not alter reward behavior, or neuroimmune and neuroendocrine activation in rats. 1668 6

Pro-inflammatory cytokines, such as interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha have been suggested to be involved in the pathophysiology of depression and in the mechanism of action of antidepressant drugs. Until now the effect of antidepressants on cytokines has been examined only in plasma, blood mononuclear cells and spleen, which reflect the activity of peripheral cytokine network. The aim of this study was to evaluate the effect of amitriptyline and its metabolite nortriptyline on the release of IL-1beta and TNF-alpha by lipopolysaccharide (LPS)-activated rat mixed glial and microglial cell cultures. LPS stimulated the release of both cytokines. The exposure of mixed glial culture to amitriptyline and nortriptyline led to a decrease in both IL-1beta and TNF-alpha release. Moreover, amitriptyline reduced LPS-stimulated IL-1beta release by microglial cultures. Although amitriptyline reduced secretion of both cytokines, the drug did not affect IL-1beta and TNF-alpha mRNAs in mixed cell cultures. Our study has shown for the first time that amitriptyline and nortriptyline administered at concentrations which may be achieved in plasma and brain structures during treatment, inhibit the secretion of IL-1beta and TNF-alpha in rat mixed glial and microglial cell cultures. The obtained results support the previous observations that antidepressants are able to reduce peripheral release of pro-inflammatory cytokines and suggest that the cytokine network may be involved in the central mechanism of action of amitriptyline and nortriptyline.
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PMID:Amitriptyline and nortriptyline inhibit interleukin-1 release by rat mixed glial and microglial cell cultures. 1596 43

Perfluorochemicals (PFC) are chemical substances that have a high solubility for oxygen. This study investigated the effect of peritoneal lavage with oxygenated PFC (O2-PFC) against hemorrhagic shock and resuscitation (HS/R). Male Sprague-Dawley rats were anesthetized and bled to a mean arterial pressure (MAP) of 30 to 35 mmHg for 120 min. The animals then were resuscitated over 20 min with an infusion of shed blood. Peritoneal lavage was performed by inflow and outflow of the PFC solution at 80 mL/h during the shock-resuscitation period. Rats were divided into four groups. Group I, HS without peritoneal lavage; Group II, HS with nitrogenated PFC (N2-PFC) lavage; Group III, HS with O2-PFC lavage; and Group IV, sham-operated rats. Seven of seven (100%) rats in Group IV and six of seven (85.7%) rats in Group III survived for 48 h, and one of seven (14.3%) rats in Group I and zero of seven rats in Group II survived (P < 0.01). In Group III rats, metabolic acidosis (assessed by blood gas analysis) and depression of intestinal blood flow (assessed by laser Doppler flowmetry) during HS were markedly ameliorated in comparison with those in Group I or Group II rats. The elevation of plasma TNF-alpha and IL-6 after HS/R were also attenuated in Group III. Histological study showed that O2-PFC lavage significantly decreased the degree of intestinal mucosal damage. We conclude that treatment with O2-PFC lavage ameliorated HS/R-induced metabolic acidosis and intestinal damage, which was associated with better mortality, possibly by preserving microvascular perfusion and maintaining oxygen metabolism.
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PMID:Peritoneal lavage with oxygenated perfluorochemical improves hemodynamics, intestinal injury, and survival in a rat model of severe hemorrhagic shock and resuscitation. 1604 89

Recently we reported that Toll-like receptor 4 (TLR4)-positive immune cells of unknown identity were responsible for the LPS-induced depression of cardiac myocyte shortening. The aim of this study is to identify the TLR4-positive cell type that is responsible for the LPS-induced cardiac dysfunction. Neither neutrophil depletion alone nor mast cell deficiency had any impact on the impairment of myocyte shortening during LPS treatment. In contrast, LPS-treated, macrophage-deficient mice demonstrated a partial reduction in shortening compared with saline-treated, macrophage-deficient mice. Because the removal of macrophages could only partially restore myocyte shortening, we also investigated the effects of removing both neutrophils and macrophages on myocyte shortening. Interestingly, endotoxemic, neutrophil-depleted, and macrophage-deficient mice had completely restored myocyte shortening. Because both macrophages and neutrophils can produce nitric oxide (NO) and TNF-alpha, we examined LPS-treated inducible NO synthase knockout (iNOSKO) mice and TNF receptor (TNFR)-deficient mice. Eliminating both TNFR1 and TNFR2 was required to restore myocyte shortening during LPS treatment, whereas iNOS deficiency had no effect. These data suggest that macrophages and to a lesser degree neutrophils cause cardiac impairment, presumably via TNF-alpha.
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PMID:Cellular and molecular mechanisms underlying LPS-associated myocyte impairment. 1617 57

To the ill patient with diabetes, the behavioral symptoms of sickness such as fatigue and apathy are debilitating and can prevent recuperation. Here we report that peripherally administered insulin-like growth factor 1 (IGF-1) attenuates LPS-dependent depression of social exploration (sickness) in nondiabetic (db/+) but not in diabetic (db/db) mice. We show that the insulin/IGF-1 mimetic vanadyl sulfate (VS) is effective at augmenting recovery from sickness in both db/+ and db/db mice. Specifically, peak illness was reached at 2 h for both VS and control animals injected with LPS, and VS mice recovered 50% faster than non-VS-treated animals. Examination of the mechanism of VS action in db/+ mice showed that VS paradoxically augmented peritoneal macrophage responsivity to LPS, increasing both peritoneal and ex vivo macrophage production of IL-1beta and IL-6 but not TNF-alpha. The effects of VS in promoting recovery from sickness were not restricted to LPS, because they were also observed after direct administration of IL-1beta. To explore the possibility that VS impairs immune-to-brain communication via vagal afferents, the vagally mediated satiety-inducing effects of cholecystokinin 8 were tested in db/+ mice. Cholecystokinin decreased food intake in saline-injected mice but not in VS-treated mice. VS also inhibited LPS-dependent up-regulation of IL-1beta and IL-6 mRNA in the brain, while increasing by 50% the cerebral expression of transcripts of the specific antagonist of IL-1 receptors IL-1RA and IL-1R2. Taken together, these data indicate that VS improves recovery from LPS-induced sickness by blocking vagally mediated immune-to-brain signaling and by up-regulating brain expression of IL-1beta antagonists.
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PMID:Inhibition of vagally mediated immune-to-brain signaling by vanadyl sulfate speeds recovery from sickness. 1621 19

The persistent activation of the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary axes in chronic stress response and in depression impairs the immune response and contributes to the development and progression of some types of cancer. This overview presents results from experimental animal models, human studies, and clinical evidence that various cellular and molecular immunological parameters are compromised in chronic stress and depression. At the cellular level, stressed and depressed patients had overall leukocytosis, high concentrations of circulating neutrophils, reduced mitogen-stimulated lymphocyte proliferation and neutrophil phagocytosis. At the molecular level, high levels of serum basal cortisol, acute phase proteins, specific antibodies against herpes simplex virus type 1 and Epstein Barr virus, plasma concentration of interleukins IL-1, IL-6, and TNF-alpha, and a shift in the balance of Th1 and Th2 immune response were observed. Both stress and depression were associated with the decreased cytotoxic T-cell and natural killer cell activities affecting the processes of the immune surveillance of tumours, and the events that modulate the development and the accumulation of somatic mutations and genomic instability. DNA damage, growth and angiogenic factors, proteases, matrix metalloproteinases, and reactive oxygen species were also related to the chronic stress response and depression. Behavioural strategies, psychological, and psychopharmacotherapeutic interventions that enhance effective coping and reduce affective distress showed beneficial effects in cancer patients. A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to novel clinical and treatment strategies in oncology.
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PMID:Stress and depression-induced immune dysfunction: implications for the development and progression of cancer. 1640 50


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