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)

Intracerebroventricular (i.c.v.) interleukin-10 (25, 50, and 100 ng/rat) effects on water intake, exploratory behaviour, and rectal temperature were evaluated in rats treated intraperitoneally (i.p.) with lipopolysaccharide (0.32, 0.64, and 0.96 mg/kg). Endotoxin administration induced fever and inhibition of thirst in water-deprived rats, and a decrease in lococomotory activity in normohydrated and water-deprived animals. Our data show that interleukin-10 during lipopolysaccharide administration controlled fever, increases exploratory behaviour, but did not reverse lipopolysaccharide inhibition of thirst. These effects suggest that fever, depression in locomotory activity but not inhibition of thirst, induced by endotoxin are influenced by interleukin-10 levels.
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PMID:Effects of interleukin-10 on water intake, locomotory activity, and rectal temperature in rat treated with endotoxin. 922 77

Escape from immune surveillance is critical for tumor progression in metastatic melanoma. We assessed the function of melanoma-derived dendritic cells (DCs) in patients presenting simultaneously with responding (rM) or progressing (pM) melanoma metastases. These rare coincidences allowed us to compare syngeneically the function of tumor DCs. CD83+ DCs were purified freshly from large responding (rDCs) or progressing (pDCs) metastases following chemoimmunotherapy. rDCs were 5 times more potent inducers of allogeneic T-cell proliferation than the pDCs that were used as control. Phenotypic analysis showed a marked depression of CD86 expression on pDCs. Culture supernatants from pM showed production of Th2-type cytokines [interleukin-10 (IL-10)], whereas a Th1 pattern [IL-2, interferon-gamma (IFN-gamma), IL-12) predominated in rM. The IL-10 detected in progressing metastases was directly derived from melanoma cells. Culture supernatants from metastases applied to DC-supported allo-MLR assays suppressed T-cell responses by 50-75% in the case of pM, but not rM. Finally, in a co-stimulation-dependent anti-CD3 tolerance assay, pDCs (but not rDCs) induced anergy in syngeneic CD4+ T cells. Anergy could be overcome by addition of IL-12 or IL-2. Our results show that melanoma-derived factors convert DC-antigen presenting cell function to tolerance induction against tumor tissue, changing tumor DCs to "silencers" of anti-tumoral immune responses.
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PMID:Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. 935 74

The mechanisms whereby trypanotolerant N'Dama cattle control infection with Trypanosoma congolense are unknown. Previous studies have suggested that the monocytes of N'Dama cattle are more highly activated during infection than those of trypanosusceptible Boran cattle. However, we have recently reported that the monocytes of Boran cattle have a reduced capacity to secrete nitric oxide during trypanosome infection. We therefore evaluated the production of nitric oxide by monocytes of trypanotolerant N'Dama cattle infected with T. congolense in response to interferon-gamma, bacterial lipopolysaccharide or trypanosome antigens. Interferon-gamma-induced nitric oxide production was decreased between days 25 and 76 of infection, while lipopolysaccharide-induced secretion of nitric oxide was increased at days 13 and again at day 76 post-infection. Trypanosome antigens did not elicit nitric oxide production. Analysis of interleukin-10 mRNA transcription in peripheral blood leucocytes revealed an increase at time points that coincided with decreased interferon-gamma-induced nitric oxide synthesis. In contrast, interferon-gamma mRNA expression was not changed during infection while tumour necrosis factor-alpha was slightly reduced at day 32 post-infection. Recombinant interleukin-10 suppressed interferon-gamma-induced nitric oxide and tumour necrosis factor-alpha secretion, but not lipopolysaccharide-induced nitric oxide secretion in cultures of peripheral blood mononuclear cells and monocytes of uninfected cattle. These results suggest that the nitric oxide response of monocytes to IFN-gamma but not lipopolysaccharide, is suppressed during infection. The kinetics of the upregulation of interleukin-10 and its biological activity indicate a possible association with the depression of nitric oxide production and control of tumour necrosis factor-alpha.
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PMID:Trypanosoma congolense infection of trypanotolerant N'Dama (Bos taurus) cattle is associated with decreased secretion of nitric oxide by interferon-gamma-activated monocytes and increased transcription of interleukin-10. 976 9

We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.
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PMID:Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice. 979 15

Peripheral (i.p.) and central (i.c.v.) injections of lipopolysaccharide (LPS) have been shown to induce brain expression of proinflammatory cytokines and to depress social behaviour in rats, increase duration of immobility and induce body weight loss. To determine if the anti-inflammatory cytokine, interleukin-10 (IL-10) is able to modulate these effects, recombinant rat IL-10 was injected in the lateral ventricle of the brain (30, 100, 300 ng/rat) prior to i.p. or i.c.v. injection of LPS (250 micrograms/kg or 60 ng/rat, respectively). Social exploration was depressed for 6 h after i.p. LPS injection. This effect was attenuated by IL-10 (30 and 100 ng) 2 h after injection, whereas the highest dose of IL-10 blocked the depression of social interaction for 6 h after LPS injection. IL-10 produced the same effects on the increase of immobility although the results did not reach significance. Social exploration was depressed 3 h after i.c.v. LPS injection, and this was accompanied by increased immobility. These effects were totally blocked by i.c.v. IL-10 (300 ng/rat). Rats lost body weight after i.c.v. LPS, and this effect was attenuated by i.c.v. IL-10. These results indicate that IL-10 is able to modulate the production and/or action of central proinflammatory cytokines.
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PMID:Central injection of IL-10 antagonizes the behavioural effects of lipopolysaccharide in rats. 1010 35

Overwhelming inflammatory immune response can result in systemic inflammation and septic shock. To prevent excessive and deleterious action of proinflammatory cytokines after they have produced their initial beneficial effects, the immune system can release several anti-inflammatory mediators, including interleukin-10, interleukin-1 receptor antagonist, and soluble tumor necrosis factor receptors, thus initiating a compensatory anti-inflammatory response syndrome. However, in vivo the delicate balance between pro- and anti-inflammatory responses is additionally controlled by the central nervous system. Therefore, proinflammatory cytokines stimulate the hypothalamic-pituitary-adrenal axis and enhance sympathetic nerve system activity. The mediators of these neuroimmune pathways can again suppress immune cell functions to control systemic inflammation. The question is, however, what happens if the immunoinhibitory CNS pathways are activated without systemic inflammation? This can result from production of cytokines in the brain following infection, injury, or ischemia or in response to various stressors (e.g., life events, depression, anxiety) or directly from brainstem irritation. The answer is that this may generate a brain-mediated immunodepression. Many animal and clinical studies have demonstrated a stress and brain cytokine mediated decrease in the cellular immune response at the lymphocyte level. More recently, the importance of monocytes in systemic immunocapacity has been shown. Monocytic inactivation with decreased capability of antigen presentation and depressed secretion of proinflammatory cytokines increases the risk of infectious complications. Interestingly, cytokines in the brain and other stressors can also generate systemic immunodepression at the monocyte level. In this scenario the catecholamine-induced release of the potent anti-inflammatory cytokine interleukin-10 is a newly discovered mechanism of the brain-mediated monocyte deactivation in addition to the "well known" immunosuppressive action of glucocorticoids. Furthermore, other neuropeptides such as alpha-melanocyte-stimulating hormone and beta-endorphin which can be released in stressful situations have also inhibitory effects on immune cells. Thus mediators of the CNS are implicated in the regulation of immune functions and may play a role in both conditioning the host's response to endogenous or exogenous stimuli and generating a "brain-mediated" immunodepression.
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PMID:Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. 1061 37

This study determined the effect of femoral nailing on the expression of monocyte Class II antigens and interleukin-10 release and sought to differentiate any differences in the release of these elements of immune reactivity in patients undergoing reamed and unreamed nailing. Thirty-two patients presenting with an acute femoral fracture were studied. In 15 patients, the femoral fracture was stabilized with a reamed technique and in 17 patients with an unreamed technique. Venous blood samples were taken at presentation, at anesthetic induction, immediately after nail insertion, and subsequently at 1, 4, and 24 hours and at 3, 5, and 7 days after surgery. Serum interleukin-10 was measured by an enzyme-linked immunosorbent assay, and monocyte human leukocyte antigen-DR expression was quantified by flow cytometry. Serum interleukin-10 release and human leukocyte antigen-DR expression on monocytes showed a clear response to the nailing procedure. The group of patients undergoing a reamed femoral nailing procedure showed significantly higher interleukin-10 release and a significant depression in the expression of human leukocyte antigen-DR on monocytes compared with those whose nail had been inserted unreamed. One patient in the reamed femoral nailing group died of adult respiratory distress syndrome 3 days after injury. Reamed intramedullary nailing appears to be associated with greater impairment of immune reactivity than is the unreamed nailing technique.
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PMID:Interleukin-10 release and monocyte human leukocyte antigen-DR expression during femoral nailing. 1081 Apr 82

Heart failure is a complex neurohumoral and inflammatory syndrome. Recent studies have shown that proinflammatory cytokines (interleukin-1, interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor) are involved in cardiac depression and in the complex syndrome of heart failure. Understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure by the use of monoclonal antibodies directed against specific cytokines to block the downhill progression of heart failure.
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PMID:Pathophysiological role of cytokines in congestive heart failure. 1116 Jul 65

There is some evidence that major depression--in particular, treatment-resistant depression (TRD)--is accompanied by activation of the inflammatory response system and that proinflammatory cytokines may play a role in the etiology of depression. This study was carried out to examine the effects of antidepressive agents, i.e., imipramine, venlafaxine, L-5-hydroxytryptophan, and fluoxetine on the production of interferon-gamma (IFN-gamma), a proinflammatory cytokine, and interleukin-10 (IL-10), a negative immunoregulatory cytokine. Diluted whole blood of fluoxetine-treated patients with TRD (mean age, 50.6+/-3.9 years) and age-matched healthy controls (mean age, 51.6+/-1.7 years) and younger healthy volunteers (mean age, 35.4+/-9.6 years) was stimulated with phytohemagglutinin (1 microg/mL) and lipopolysaccharide (5 microg/mL) for 48 hours with and without incubation with the antidepressants at 10-6 M and 10(-5) M. IFN-gamma and IL-10 were quantified by means of enzyme-linked immunoassays. The ratio of IFN-gamma to IL-10 production by immunocytes was computed because this ratio is of critical importance in determining the capacity of immunocytes to activate or inhibit monocytic and T-lymphocytic functions. All four antidepressive drugs significantly increased the production of IL-10. Fluoxetine significantly decreased the production of IFN-gamma. All four antidepressants significantly reduced the IFN-gamma/IL-10 ratio. There were no significant differences in the antidepressant-induced changes in IFN-gamma or IL-10 between younger and older healthy volunteers and TRD patients. Tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-noradrenaline reuptake inhibitors, as well as the immediate precursor of serotonin, have a common, negative immunoregulatory effect by suppressing the IFN-gamma/IL-10 production ratio. It is suggested that the therapeutic efficacy of antidepressants may be related to their negative immunoregulatory effects.
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PMID:Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. 1127 Sep 17

It is well established that the hypothalamic-pituitary-adrenal axis (HPA) is activated by both external and internal stressors which result in the hypersecretion of adrenal glucocorticoids. In major depression the prolonged elevation of the glucocorticoid concentration leads to a desensitisation of the central glucocorticoid receptors and probably those receptors located on macrophages. These changes may account for the observation that many aspects of cellular immunity are activated in depression (for example, the increased release of pro-inflammatory cytokines from activated macrophages in the periphery and brain, and the increased release of acute phase proteins from the liver) even though other aspects of immunity (for example, natural killer cell activity and T-cell replication) are depressed. It is also known that some of the pro-inflammatory cytokines are potent activators of the HPA axis. Evidence is provided that the consequences of the hypersecretion of glucocorticoids and pro-inflammatory cytokines result in the malfunctioning of noradrenergic and serotonergic neurotransmission in the brain, changes which are reflected in the major symptoms of depression. Support for this view is provided by observations of the effects of some of these cytokines in non-depressed individuals being treated with pro-inflammatory and related cytokines for cancer. This has led to the hypothesis that depression is a form of sickness behaviour which forms the basis of the macrophage theory of depression. The review concludes with a discussion of the role of antidepressants in attenuating the adverse effects of glucocorticoids and pro-inflammatory cytokines on central neurotransmission. Although the precise mechanisms whereby antidepressants these changes is uncertain, there is evidence that they reduce the release of pro-inflammatory cytokines from activated macrophages and thereby facilitate the feedback inhibition of the HPA axis; this results in a reduction in the release of glucocorticoids from the adrenal glands. In addition, many antidepressants have been shown to increase the release of endogenous cytokine antagonists such as interleukin-1 receptor antagonist and interleukin-10. Evidence is also presented to show that different classes of antidepressants act as cyclooxygenase inhibitors which, by lowering the concentration of inflammatory prostaglandins in the brain, reduce the detrimental impact of the inflammatory changes on neurotransmitter function. An advantage of the macrophage hypothesis is that it extends the biogenic amine hypothesis of depression to take account of changes in the endocrine and immune systems which also play a crucial role in the aetiology of depression. In addition, the macrophage hypothesis may broaden the basis of understanding the mechanism of action of antidepressants.
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PMID:The immune system, depression and the action of antidepressants. 1138 77


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