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)

NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.
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PMID:Insulin in sepsis and septic shock. 1462 Oct 41

Some studies suggest that inaccuracy in recognizing and describing emotional states, combined with a highly descriptive mode of expression, as in alexithymia, may influence the immune response. We therefore investigated in healthy women the relationship between alexithymia and circulating levels of IL-1, IL-2 and IL-4. Seventeen mentally and physically healthy women aged between 20 and 25 years completed psychological questionnaires to assess alexithymia (Toronto Alexithymia Scale: TAS) and depressed mood (Hospital Anxiety and Depression Scale: HAD). Serum concentrations of IL-1, IL-2 and IL-4 were measured by ELISA. We found a significant positive correlation between serum levels of IL-4 and TAS score (r=0.55; p=0.021) and between factor 1 of the TAS (difficulty in identifying feelings) and IL-4 (r=0.57; p=0.017) while serum IL-1 and IL-2 were not detected in ten and six patients, respectively. Although there was a significant correlation between age and IL-4 levels, a linear regression with BMI, age, depressed mood and TAS as independent variables showed that only alexithymia could predict significantly increased levels of IL-4. Alexithymia and difficulty in identifying feelings could be associated with increased levels of IL-4 which may result in chronic impairment of pro/anti-inflammatory cytokine balance with psychological and somatic consequences. Nevertheless, these intriguing findings would deserve replication and extension in a larger sample of subjects.
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PMID:Correlation between serum levels of interleukin-4 and alexithymia scores in healthy female subjects: preliminary findings. 1474 98

The purpose of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake and depression. The sample consisted of 150 elderly males from the island of Crete. The subjects were survivors of the Greek Seven Countries Study group. The mean age was 84 years. The number of subjects with complete data on all variables studied was 63. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the short form of the Geriatric Depression Scale (GDS-15). Depression correlated negatively with adipose tissue alpha-linolenic acid (C18:3n-3). Depressed subjects had significantly reduced (-10.5%) adipose tissue C18:3n-3 levels than non-depressed subjects. The observed negative relation between adipose tissue C18:3n-3 and depression, in the present study, appears to indicate increasing long-term dietary C18:3n-3 intakes with decreasing depression. This agrees with findings of other studies indicating an inverse relation between depression and consumption of fish and n-3 polyunsaturated fatty acids. This is the first literature report of a relation between adipose tissue C18:3n-3 and depression. Furthermore, this is the first report of a relation between adipose PUFA and depression in an elderly sample. Depression has been reported to be associated with elevated cytokines, such as, IL-1, IL-2, IL-6, INF-gamma and INF-alpha. Fish oil and omega-3 fatty acids, on the other hand, have been reported to inhibit cytokine production. The observed negative relation between adipose C18:3n-3 and depression, therefore, may stem from the inhibiting effect of C18:3n-3 or its long-chain metabolites on cytokine synthesis.
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PMID:Depression and adipose polyunsaturated fatty acids in the survivors of the Seven Countries Study population of Crete. 1512 Jul 12

Male CD-1 mice were administered interleukin-1beta (IL-1beta) and bacterial endotoxin (lipopolysaccharide, LPS) and subsequently tested in the tail suspension test (TST), the Porsolt forced swim test (FST), and in the open field. IL-1beta (100, 300 and 1000 ng/mouse) injected intraperitoneally (i.p.) 90 min before the test induced a dose-dependent increase in the time spent immobile in the TST and the time spent floating in the FST. These responses were statistically significant only at the higher doses of IL-1beta (300 and 1000 ng). Nevertheless, all three doses of IL-1beta significantly decreased line crossings and rears in the open field and depressed food intake and body weight. Very similar effects were induced by LPS. Doses of 1 and 5 mug i.p. increased immobility time in the TST and floating time in the FST, but the same doses strongly depressed locomotor activity and body weight. These results indicate that both IL-1beta and LPS can induce depression-like effects in the TST and the FST. However, the doses necessary to induce these changes reduced feeding and activity in an open field, so that the effects observed in the FST and TST could be attributed to a general reduction in locomotor activity. Thus the results obtained in these two animal tests commonly used to test antidepressant properties do not provide strong support for an IL-1 hypothesis of depression.
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PMID:Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice. 1598 28

Interleukin-1beta is released at the periphery during infection and acts on the nervous system to induce fever, neuroendocrine activation, and behavioral changes. These effects are mediated by brain type I IL-1 receptors. In vitro studies have shown the ability of interleukin-1beta to activate mitogen-activated protein kinase signaling pathways including p38, c-Jun N-terminal kinase and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In contrast to other mitogen-activated protein kinases, little is known about ERK1/2 activation in the rat brain in response to interleukin-1beta. The aim of the present study was therefore to investigate spatial and temporal activation of ERK1/2 in the rat brain after peripheral administration of interleukin-1beta using immunohistochemistry to detect the phosphorylated form of the kinase. In non-stimulated conditions, phosphorylated ERK1/2 immunoreactivity was observed in neurons throughout the brain. Administration of interleukin-1beta (60 microg/kg, i.p.) induced the phosphorylation of ERK1/2 in areas at the interface between brain and blood or cerebrospinal fluid: meninges, circumventricular organs, endothelial like cells of the blood vessels, and in brain nuclei involved in behavioral depression, fever and neuroendocrine activation: paraventricular nucleus of the hypothalamus, supraoptic nucleus, central amygdala and arcuate nucleus. Double labeling of phosphorylated ERK1/2 and cell markers revealed the expression of phosphorylated ERK1/2 in neurons, astrocytes and microglia. Since phosphorylated ERK1/2 was found in structures in which type I IL-1 receptor has already been identified as well as in structures lacking this receptor, activation of ERK1/2 is likely to occur in response to both direct and indirect action of interleukin-1beta on its target cells.
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PMID:Signaling pathways of interleukin-1 actions in the brain: anatomical distribution of phospho-ERK1/2 in the brain of rat treated systemically with interleukin-1beta. 1603 91

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

The therapeutic use of interferon-alpha (IFN-alpha), a proinflammatory cytokine, is known to cause various neuropsychiatric adverse effects. In particular, depression occurs in 30-45% of patients, frequently interrupting treatment. IFN-alpha-treated animals also show depression-like behaviors. However, mechanisms underlying the depression caused by IFN-alpha remain to be defined. Recently, a decrease in adult hippocampal neurogenesis was revealed as a possible neuropathological mechanism of depression. Therefore, we investigated the effect of subchronic IFN-alpha treatment on neurogenesis in the adult rat dentate gyrus (DG). Immediately after the administration of IFN-alpha for 1 week, a decrease in the number of 5-bromo-deoxyuridine-labeled proliferating cells was observed in the DG; however, no effect was detected on the expression of mature neuronal phenotype in the newly formed cells 3 weeks later. Also, an increase in the level of interleukin-1beta (IL-1beta), a major proinflammatory cytokine, was observed in the hippocampus following the administration of IFN-alpha. Furthermore, coadministration of an IL-1 receptor antagonist completely blocked the IFN-alpha-induced suppression of the cell-proliferative activity in the DG. Our results indicate that IFN-alpha suppresses neurogenesis in the DG, and that IL-1beta plays an essential role in the suppression. The decreased cell proliferation caused by IFN-alpha-induced IL-1beta may be responsible, at least in part, for IFN-alpha-induced depression.
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PMID:Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus. 1682 90

The purpose of this study was to investigate the clinical effects of balneotherapy in the treatment of Fibromyalgia Syndrome (FMS) and to determine if balneotherapy influences serum levels of inflammation markers, IL-1, PGE2 and LTB4. 24 primary fibromyalgia female patients diagnosed according to American College of Rheumatology criteria were included to the study. Their ages ranged between 33 and 55 years. FMS patients were randomly assigned in two groups as, group 1 (n = 12) and group 2 (n = 12). Group 1 received 20-min bathing, once in a day for five days per week. Patients participated in the study for 3 weeks (total of 15 sessions) in Denizli. Group 2 did not receive balneotherapy. FMS patients were evaluated by tenderness measurements (tender point count and algometry), Visual Analogue Scale, Beck's Depression Index, Fibromyalgia Impact Questionnaire. Ten healthy women recruited group three as the controls. Serum PGE2, LTB4 and IL1-alpha levels were measured in all three groups. The biochemical measurements and clinical assessments were performed before and at the end of general period of therapy. Statistically significant alterations in algometric score, Visual Analogue score, Beck's Depression Index and PGE2 levels (P < 0.001), numbers of tender points (P < 0.01) and Fibromyalgia Impact Questionnaire score (P < 0.05) were found after the balneotherapy between group 1 and 2. Mean PGE2 level of FMS patients were higher compared to healthy control group (P < 0.0001) and decreased after the treatment period, only in group 1 (P < 0.05). As in the group 2 and 3, detectable IL-1 and LTB4 measurements were insufficient, statistical analysis was performed, only in group 1. After balneotherapy IL-1 and LTB4 significantly decreased in group 1 (P < 0.05). In conclusion, balneotherapy is an effective choice of treatment in patients with FMS relieving the clinical symptoms, and possibly influencing the inflammatory mediators.
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PMID:Effects of balneotherapy on serum IL-1, PGE2 and LTB4 levels in fibromyalgia patients. 1703 35

Cytokine-induced sickness behavior was recognized within a few years of the cloning and expression of interferon-alpha, IL-1 and IL-2, which occurred around the time that the first issue of Brain, Behavior, and Immunity was published in 1987. Phase I clinical trials established that injection of recombinant cytokines into cancer patients led to a variety of psychological disturbances. It was subsequently shown that physiological concentrations of proinflammatory cytokines that occur after infection act in the brain to induce common symptoms of sickness, such as loss of appetite, sleepiness, withdrawal from normal social activities, fever, aching joints and fatigue. This syndrome was defined as sickness behavior and is now recognized to be part of a motivational system that reorganizes the organism's priorities to facilitate recovery from the infection. Cytokines convey to the brain that an infection has occurred in the periphery, and this action of cytokines can occur via the traditional endocrine route via the blood or by direct neural transmission via the afferent vagus nerve. The finding that sickness behavior occurs in all mammals and birds indicates that communication between the immune system and brain has been evolutionarily conserved and forms an important physiological adaptive response that favors survival of the organism during infections. The fact that cytokines act in the brain to induce physiological adaptations that promote survival has led to the hypothesis that inappropriate, prolonged activation of the innate immune system may be involved in a number of pathological disturbances in the brain, ranging from Alzheimer's disease to stroke. Conversely, the newly-defined role of cytokines in a wide variety of systemic co-morbid conditions, ranging from chronic heart failure to obesity, may begin to explain changes in the mental state of these subjects. Indeed, the newest findings of cytokine actions in the brain offer some of the first clues about the pathophysiology of certain mental health disorders, including depression. The time is ripe to begin to move these fundamental discoveries in mice to man and some of the pharmacological tools are already available to antagonize the detrimental actions of cytokines.
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PMID:Twenty years of research on cytokine-induced sickness behavior. 1708 43


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