UMLS:C0011570 - FACTA Search

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

A depression-like state was induced by chronic (3-week) exposure of Wistar rats to a very mild, unpredictable stress which is a model of depression, developed by Willner's group. Five-week daily administration of imipramine reversed the stress-induced deficit in sucrose consumption. Eight-week stress induced an increase in the ability of splenocytes to produce interleukin 1 (IL-1) and interleukin 2 (IL-2) and to proliferate after stimulation with concanavalin A. Antidepressant effects of imipramine were accompanied by a decrease in the ability of splenocytes to produce IL-1 and IL-2 and to proliferate. Administration of imipramine alone did not modify the activity of those cells.
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PMID:Effect of chronic treatment with imipramine on interleukin 1 and interleukin 2 production by splenocytes obtained from rats subjected to a chronic mild stress model of depression. 911 92

There is a strong interrelationship between the immune system, the central nervous system and psychological processes that are suggested to play a pivotal role in the pathogenesis of psychiatric disorders. In schizophrenia and depression, activation of the immune system has been observed repeatedly. Cytokines play a key role in immune activation. They are actively transported into the CNS, but also released from activated glia cells. Cytokines activate glia cells in the CNS to produce other cytokines, and a cascade of cytokine effects may be initiated by this mechanisms. During the past few years, the influence of the cytokines on dopaminergic, noradrenergic and serotonergic neurotransmission and also on the hormones of the hypothalamus-pituitary-adrenal axis has been elucidated. It suggests a pivotal role in psychological processes and psychiatric disorders. For example, in schizophrenia the IL-2 cerebrospinal fluid concentration shows a stronger relationship to the relapse probability than catecholamine metabolites. Although the hypersecretion of IL-2 in schizophrenia and of IL-6 in depression are suggested to play key roles for these disorders, a specificity of certain cytokines for certain psychiatric disorders seems unlikely. Psychomotor, sleep and sickness behavior are influenced by IL-1, disturbances of memory and attention by IL-2, but also by TNF-alpha. From the distribution of cytokine receptors in the CNS conclusions can be drawn regarding the influence of cytokines on psychological processes. The finding that norepinephrine stimulates activated astrocytes to produce IL-6 implies that the cytokine cascade may be activated by neuronal processes under certain conditions. This can lead to a molecular biological explanation of the influences of stress on the immune system. Lastly, influences of the cytokines on blood-brain barrier disturbances and further consequences resulting from the role of the cytokine network in the CNS are discussed.
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PMID:[Role of the cytokine network in the CNS and psychiatric disorders]. 913 17

The development of murine contact hypersensitivity is influenced by hair follicle cycling. Here, we have examined hair cycle-associated fluctuations of murine contact photosensitivity (CPS) to tetrachlorosalicylanilide (TCSA) and its immunologic mechanism(s). When the CPS outcome was monitored in correlation with their spontaneous, synchronized hair cycling, mice aged 8 and 14 weeks, with most of their hair follicles in telogen, exhibited strong CPS responses, whereas 4-, 11-, and 16-week-old mice with a predominance of anagen follicles in a large area of their integument exhibited lower responses. This suggests that the development of CPS is inhibited in mice with anagen hair follicles. Antigen-specific, T-cell receptor V beta 7+ suppressor T cells, which are recognized to down-regulate the CPS response to TCSA, were not generated in sensitized anagen mice. Culture supernatants of epidermal cells derived from mice with anagen hair follicles contained factor(s) that suppress in vivo the development of CPS. It was found that levels of mRNA for tumor necrosis factor alpha (TNF alpha) were markedly decreased in epidermal cells from early anagen to telogen mice, whereas message for IL-1 receptor antagonist (IL-1ra) was transcribed increasingly during this hair cycling. These findings suggest that altered keratinocyte production of these cytokines is involved in mediating the anagen-associated depression of CPS.
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PMID:Spontaneous hair follicle cycling may influence the development of murine contact photosensitivity by modulating keratinocyte cytokine production. 922 8

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 proinflammatory cytokines which are released by activated accessory immune cells during the course of an infection have profound effects on the brain. These effects include activation of the hypothalamic-pituitary-adrenal axis, fever and behavioral depression. They are mediated by cytokines which are synthesized and released in the brain, in response to peripherally released cytokines. Glucocorticoids have potent regulatory effects on the synthesis of cytokines by activated macrophages and monocytes. These hormones are also able to regulate the synthesis and action of cytokines in the brain, as demonstrated by the sensitizing effects of adrenalectomy and the depressing effects of stress on the increased cytokine and interleukin-1 beta converting enzyme gene expression that occurs in response to lipopolysaccharide in mice. Preliminary experiments indicate that another way glucocorticoids can contribute to down regulation of the IL-1 system is by increasing the expression of the type II IL-1 receptor in the brain. The regulatory effects of glucocorticoids on cytokine expression in the brain have functional consequences, as demonstrated by the enhanced sensitivity of adrenalectomized animals to the behavioral actions of centrally administered LPS and IL-1. The effects of adrenalectomy are inhibited by compensation with a corticosterone implant and they are mimicked by administration of the type II glucocorticoid receptor, RU 38486. The regulatory role of glucocorticoids on the expression and action of cytokines in the brain makes these hormones and their mechanisms of action key targets for therapeutic interventions in psychopathology and neuropathology.
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PMID:Regulation of cytokine gene expression in the central nervous system by glucocorticoids: mechanisms and functional consequences. 926 51

Recent studies indicate beneficial effects of androgen depletion in male mice, before trauma-hemorrhage on cell-mediated immunity following soft-tissue trauma and hemorrhagic shock. Nonetheless, it remains unknown whether androgen receptor blockade following the insult has any salutary effects. To study this, male C3H/HeN mice were either sham-operated or subjected to soft-tissue trauma (i.e., 2.5 cm midline laparotomy) followed by hemorrhagic shock (blood pressure 35 +/- 5 mmHg for 90 min) and then adequately resuscitated (shed blood and lactated Ringer's). Immediately after the completion of resuscitation, as well as 24 and 48 h thereafter, the animals received either vehicle, 10 mg/kg body weight (BW) flutamide or 25 mg/kg BW flutamide subcutaneously. At 72 h after resuscitation, all animals were killed. The spleens and peritoneal macrophages (M phi) were then harvested and cultures established to determine IL-2 and IL-3 release, splenocyte proliferative capacity, as well as splenic and peritoneal M phi IL-1 release. Moreover, plasma testosterone and corticosterone levels were measured. Our results indicate that trauma-hemorrhage resulted in significant depression of splenocyte and M phi functions in vehicle-treated and animals receiving 10 mg/kg BW flutamide. Treatment with 25 mg/kg BW flutamide following trauma-hemorrhage, however, resulted in levels of cytokine release which were comparable with those found in sham-operated animals. No significant alterations in plasma corticosterone and testosterone levels were observed in any of the experimental groups. These findings indicate that short-term therapy of males with the androgen receptor blocker, flutamide at 25 mg/kg BW, following trauma-hemorrhage has protective effects on immune functions. This protective effect is dose dependent, since 10 mg/kg BW flutamide did not produce significant salutary effects. Thus, flutamide represents a novel and safe agent for improving the depressed functions in male trauma patients suffering severe blood loss.
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PMID:Flutamide: a novel agent for restoring the depressed cell-mediated immunity following soft-tissue trauma and hemorrhagic shock. 932 24

Recent studies suggest beneficial effects of castration before soft tissue trauma and hemorrhagic shock on splenocyte immune functions. Nonetheless, it remains unknown whether this effect of testosterone depletion is limited to splenocytes or is a generalized effect on immune function. The present study was therefore carried out to determine whether androgen depletion before trauma-hemorrhage also has salutary effects on splenic and peritoneal macrophage as well as on Kupffer cell function, as indicated by interleukin (IL)-1 and IL-6 release. Male C3H/HeN mice were castrated or sham-castrated 2 wk before the experiment and were killed at 24 h after trauma-hemorrhage and resuscitation. Significant depression of macrophage IL-1 and IL-6 release was only observed in sham-castrated mice, as opposed to normal levels of cytokine release from castrated animals after trauma-hemorrhage. In addition, only sham-castrated animals showed significantly increased levels of IL-6 release from Kupffer cells, which is believed to contribute to the systemic inflammatory response to trauma-hemorrhage. These observations suggest that the beneficial effects of androgen depletion before trauma-hemorrhage are not limited to splenocyte immune functions but are more global in nature. These results in surgically castrated animals suggest that androgen-blocking agents should be studied for their potential to reverse the immunodepression associated with trauma-hemorrhage.
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PMID:Male sex steroids are responsible for depressing macrophage immune function after trauma-hemorrhage. 935 78

There is now some evidence that major depression is accompanied by an immune response with an increased production of pro-inflammatory cytokines, such as interleukin 1(IL-1), IL-6 and interferon gamma (IFN-gamma). The aims of the present study were to examine serum IL-6, IL-1 receptor antagonist (IL-1Ra), IL-6R, Clara cell protein (CC16) and the soluble CD8 (sCD8) molecule in chronic, treatment resistant depression (TRD) both before and after subchronic treatment with antidepressants. Serum IL-6 and IL-1Ra were significantly higher in subjects with major depression and TRD than in normal controls. Subchronic treatment with antidepressants had no significant effects on serum IL-6, IL-1Ra, CC16 or sCD8, but reduced serum sIL-6R levels significantly. There were significant and positive correlations between serum IL-6, on the one hand, and sIL-6R, IL-1Ra, sCD8, number of peripheral blood leukocytes, neutrophils, CD2(+)T and CD19(+)B cells (all positive) and serum zinc (negative), on the other. These results suggest that: (1) major depression and TRD are accompanied by an activation of the monocytic arm of cell-mediated immunity; (2) the latter may be related to the immune an acute phase response in major depression; and (3) the above disorders may persist despite successful antidepressive treatment.
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PMID:Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. 936 46

Interleukin (IL)-1, IL-2 and IL-6 influence central monoamine activity in a cytokine-specific manner. We demonstrated that whereas IL-2 increased hypothalamic and hippocampal norepinephrine (NE) utilization, and DA turnover in the prefrontal cortex, IL-6 induced profound elevations of serotonin (5-HT) and mesocortical dopamine (DA) activity in the hippocampus and prefrontal cortex [S. Zalcman, J.M. Green-Johnson, L. Murray, D.M. Nance, D.G. Dyck, H. Anisman, A. H. Greenberg, Cytokine-specific central monoamine alterations following IL-1, -2 and -6 administration, Brain Res. 643 (1994) 40-49]. IL-1, in contrast, induced a wide range of central monoamine alterations. We presently report that these cytokines also differentially influence behavior. Profound reductions in non-ambulatory and ambulatory exploration were induced in BALB/c mice following IL-1 administration. In contrast, IL-2-treated mice displayed significant increases in the time spent engaged in non-ambulatory exploration, digging, rearing (particularly the number of free rears), and in the investigation of a novel stimulus (i.e., increased number and duration of stimulus contacts). IL-6-treated mice, moreover, exhibited significant increases in the time spent engaged in ambulatory exploration, digging and rearing (particularly the number of free rears, which tended to be of short duration). Modest increases in locomotion and grooming were also observed in IL-6-treated animals. Plasma corticosterone levels did not vary significantly as a function of IL-6 treatment. Hence, cytokine-specific behavioral-activating effects were induced following administration of IL-2 and IL-6. We suggest that these effects have adaptive significance and relevance to sickness behavior; however, pathological outcomes (e.g., schizophrenia, anxious-like states, anxious depression, motor abnormalities) could develop should these cytokines be overproduced or dysregulated.
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PMID:Interleukin-2 and -6 induce behavioral-activating effects in mice. 980 16

IL-1alpha and IL-1beta have potent effects on the central nervous system resulting in fever, activation of the hypothalamic-pituitary-adrenal axis and behavioural depression. These effects have mainly been studied in rats, using recombinant human and mouse IL-1. Because IL-1alpha and IL-1beta show some species specificity in the potency of their biological activities, the objective of the present work was to directly compare the effects of recombinant rat IL-1alpha and IL-1beta in the rat system as a first step to dissect out the mechanisms that are involved in these effects. In vitro, recombinant rat IL-1alpha and IL-1beta bound with the same affinity as human IL-1 to the rat insulinoma Rin m5F cell line that mainly expresses type I IL-1 receptors. This binding activated IL-1 receptors, as shown by induction of the synthesis of TNF-alpha mRNA. In vivo, recombinant rat IL-1alpha and IL-1beta enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtained at doses 100-1,000 fold lower when IL-1 was injected centrally than when it was administered peripherally, indicating that they are centrally mediated. The relative potencies of recombinant rat IL-1alpha and IL-1beta were not the same depending on the endpoint and the route of injection, indicating that different mechanisms are likely to be involved in the various effects of IL-1 on the brain.
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PMID:Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta. 983 Nov 77

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