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)

Previous studies of psychopathological populations and populations challenged by significant life events have shown that high levels of anxiety and depression are associated with impaired cellular immunity. However, less is known about the sources and psychoimmunological relevance of subclinical variations in distress in healthy populations faced with typical levels of life stress. In the present study, we examined the relations of state distress to T-cell function and in vivo cytokine levels in 40 male college freshmen on two occasions. In addition, we assessed the possible contribution of dispositional determinants of distress to immune-related differences in mood. Relative to characteristically less anxious subjects, subjects who were characteristically more anxious (but subclinically anxious) had more anxious mood and had significantly lower lymphocyte proliferative responses to the mitogen concanavalin A (Con A) as well as lower levels of circulating interleukin-1 beta. In addition, subjects with more negative attributional styles for bad events exhibited reduced Con A-stimulated T-cell responses and lower levels of circulating interleukin-2. Finally, subjects who were more depressed (but subclinically depressed) also had reduced blastogenic responses. Individual differences in cortisol and beta-endorphin were not shown to mediate these relationships. The present study provides evidence that dispositionally related variations in distress in psychiatrically healthy, relatively unstressed college males have immunological correlates that suggest altered T-cell and macrophage activity.
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PMID:Reduced cytokine levels and T-cell function in healthy males: relation to individual differences in subclinical anxiety. 769 16

An excess mortality for violence (suicides and injuries) has been observed following the use of cholesterol-lowering drugs. It has been suggested that low cholesterol is associated with depression by modifying the serotonin metabolism. In this paper, a new hypothesis concerning the association among serum lipids, depression, and atherosclerosis is proposed. The hypothesis is based on epidemiologic evidence concerning serum lipids, depression, violent deaths, and atherosclerosis. It is also based on previous results concerning a cytokine, interleukin-2. Recent observations indicate that interleukin-2 has an important role in lipid metabolism, depression, and atherosclerosis.
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PMID:Hypothesis: low serum cholesterol, suicide, and interleukin-2. 863 24

Chronic exposure of humans to benzene (BZ), a widely used industrial chemical and a ubiquitous environmental pollutant, causes aplastic anemia and acute myeloid leukemia. The purpose of the studies reported here was to determine whether the observed depression of bone marrow (BM) cellularity in mice administered benzene was reflected in a suppression of development of all of the hematopoietic lineages and to confirm the ability of interleukin-1 alpha (IL-1 alpha) to prevent BZ-induced BM cell depression. We report that BZ, administered twice per day for 2 days to C57B1/6J mice at a dose of 600 mg/kg body weight, caused a significant depression of the total number of nucleated BM cells per femur when measured on day 3. The observed depression reflects a complex situation that represents the net effect of a decrease in the total number of cells of the lymphocytic and erythroid lineages, along with an increase in the number of intermediate and terminally differentiated cells of the granulocytic lineage. An experiment to monitor the effects of BZ over a 7-day period showed a progressive depressive effect on the lymphocytes and an initial depression of the erythroid cells at day 3 that remained constant until day 7. Conversely, the numbers of intermediate and terminally differentiated granulocytes progressively increased over the 7 days. The BM appeared to recover from the depressive effects of BZ immediately upon cessation of exposure, as the number of nucleated BM cells began to rise by day 5 and was equal to that of the control group by day 7. The results expand our earlier finding (Renz and Kalf 1991) that the overall depression of BM cellularity occurs because of an inability of the stromal fibroblast to produce colony-stimulating factors essential for stem and progenitor cell survival. This results from inhibition by the BZ metabolite, hydroquinone (HQ), of the processing of pre-IL-1 alpha to the mature cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A morphological analysis of the short-term effects of benzene on the development of the hematological cells in the bone marrow of mice and the effects of interleukin-1 alpha on the process. 771 69

Acute renal failure (ARF) is a common manifestation of a septic condition which very often complicates surgical and traumatic events. The release of endotoxin, a lipopolysaccharide (LPS) from the cell wall of Gram-negative bacteria, and subsequently of numerous host mediators, is the initiating event of sepsis syndrome and eventually of septic shock. Particularly interesting is the observation that not only endotoxins but also Staphylococcus aureus which does not produce endotoxins induce the same cardiovascular changes of septic shock. The main aspect of septic shock is the inadequate oxygen supply to the body tissues. However, despite the documented myocardial depression in the course of septic shock, myocardial ischaemia is not to be considered a contributing factor, and the coronary blood flow is normal or even increased. Protein hypercatabolism can be at best only limited; in any case the optimal protein-sparing effect was observed with 1.5 g/kg proteins. Recently monoclonal antibodies to endotoxin core glycolipid have been developed; they are: (a) E5, a murine IgM anti-lipid A monoclonal antibody; (b) HA-1A, a human monoclonal antibody to endotoxin core glycolipid. In conclusion, hypercatabolic septic patients should be managed in an intensive care environment where a continuous monitoring of fluids, electrolytes, and acid-base disorders can be achieved. Surgical search of septic foci, and wide-spectrum antibiotic therapy are fundamental measures to combat cytokine and vasodilator production which impair tissue perfusion and create the premise of a shock status complicated by lactic acidosis. Dialysis treatment is a further complementary but fundamental approach that allows a large fluid and nutritional intake and a continuous correction of electrolyte and acid-base disorders.
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PMID:Basic therapeutic requirements in the treatment of sepsis in acute renal failure. 780 Feb 55

Phenotype and release of IL1 alpha, IL6 and TNF alpha were examined in monocytes derived from 14 healthy donors and 24 tumour patients in a long-term culture using immunohistochemical, RNA in situ hybridization and ELISA techniques. After stimulation with LPS and IFN-gamma, blood monocytes and resulting macrophages showed an overall decrease in cytokine release from the 6th to the 48th day of culture, both with and without HIV infection. HIV infection provided a strong stimulus for IL6 production and a weak stimulus for IL1 alpha production, whereas TNF alpha release decreased after HIV infection. Non-HIV-infected monocytes/macrophages from patients with malignancies showed significantly reduced cytokine production after stimulation, in comparison with monocytes/macrophages from healthy subjects. In vitro HIV infection of monocytes from tumour patients caused severe depression of cytokine production during the whole time of observation. In all experiments a parallel was observed between the extent of cytokine release and the presence of young/early inflammatory macrophages as identified by the antibody MAC387/27E10 in situ. In contrast, cytokine expression assessed semiquantitatively by immunohistochemical staining in situ showed discordant development, since it increased during long-term culture, while supernatant concentrations of cytokines declined. Simultaneously, significant cytokine RNA levels could be found in macrophages from the 6th to the 24th day of culture, as detected by in situ hybridization. After 48 days of culture, no more cytokine RNA was detectable, while macrophages continued to exhibit distinct immunohistochemical positivity for cytokine antibodies. From these results, it is concluded that macrophages kept in culture for a long period become inhibited in their secretion. HIV has an ambivalent effect on cytokine production in Mo/Mac, resulting in an increase in IL6 and IL1 as well as a decrease in TNF alpha production. Mo/Mac of non-HIV-infected tumour patients show significantly reduced cytokine production in comparison with Mo/Mac from healthy subjects. The sum of the HIV infection in vitro and the tumour burden results in a dramatic reduction in cytokine release in Mo/Mac. This finding may provide a possible explanation for the specific aggressive behaviour of non-Hodgkin's lymphoma and Hodgkin's disease in AIDS.
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PMID:In vitro analysis of HIV- and non-HIV-infected monocytes/macrophages from healthy subjects and patients with malignant tumours. 780 Sep 44

In utero exposure of Long Evans rats to low dosages of diazepam has previously been found to result in depression of cellular and humoral immune responses until adulthood, with marked changes in cytokine release by splenocytes and splenic macrophages. In order to assess the significance of these alterations in immune cells with regard to host resistance, we investigated the resistance of adult offspring towards Trichinella spiralis. Time-pregnant rats were treated with diazepam (1.25 mg/kg/day) or vehicle from gestational day 14 to 20. Male offspring were infected with T. spiralis at 2 months of age. This infection model tests the participation of T- and B-cell populations and of macrophages. Prenatally diazepam-exposed animals exhibited an impaired defence towards T. spiralis. The number of muscle larvae was increased as determined in digested carcasses and by morphometric analysis of the tongue. Moreover, antibody titers were altered, i.e., IgG was decreased and IgA was elevated in the prenatally diazepam-exposed group. These results demonstrate an impaired defense towards T. spiralis in adult rats after prenatal exposure to diazepam.
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PMID:Impaired host resistance to Trichinella spiralis as a consequence of prenatal treatment of rats with diazepam. 780 25

The epithelial lining of the airways is subject to injury through several processes, including infections, bronchiolitis, and fume exposures. Because airway fibrin deposition influences the course of local injury, we examined how two inflammatory cytokines influenced fibrin formation and clearance in human tracheal epithelial cells (TEC). TEC were treated with transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). TNF-alpha increased release of tissue factor (TF)-related procoagulant activity that, through generation of factor Xa, promotes assembly of the prothrombinase complex at the cell surface. Fibrinolytic activity was plasminogen dependent and due to both urokinase (uPA) and tissue plasminogen activator (tPA). The cells expressed plasminogen activator inhibitor 1 (PAI-1), but relatively little PAI-2. Depression of fibrinolysis by TGF-beta correlated with increased PAI-1. Conversely, TNF-alpha increased plasminogen activator (PA) activity due to increased uPA. Fibrinolytic activity was inhibited by actinomycin D and cyclohexamide, but changes in mRNAs for uPA, tPA, PAI-1, and TF by either cytokine were not appreciable. PAI-2 mRNA was not found. The data indicate that TGF-beta decreases the fibrinolytic capacity of TEC, suggesting that this cytokine promotes fibrin retention. TNF-alpha increases expression of both procoagulant and fibrinolytic activities; this differential regulation could favor both pericellular fibrin formation and dissolution.
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PMID:Effects of TGF-beta and TNF-alpha on procoagulant and fibrinolytic pathways of human tracheal epithelial cells. 781 Jun 74

Acute Plasmodium yoelii murine malaria is associated with a marked depression of splenic T cell responses. The present study was undertaken to address the question if a defect in T cell proliferation results from a relative increase of a non-T cell population in the spleen or real biological changes occurring in T cells of the spleen after infection. When animals were acutely infected, the splenic cells responded poorly to cross-linked anti-CD3 mAb, Con A, and PWM stimulation. At this stage, a very limited array of cytokine was expressed. We failed to detect the transcripts for IL-2R p55, IL-2, IL-6, IL-10, and IFN-gamma in mice with acute P. yoelii malaria irrespective of the number of splenocytes subjected to RT-PCR. In contrast, late in the infection when mice cleared the parasites and became resistant to reinfection, mRNAs for the above cytokines as well as for IL-4, IL-5, GM-CSF, and TNF-alpha were detectable. During this late phase of infection, lymphocytes proliferated vigorously in response to TCR- and T cell mitogen-mediated stimulation. Surprisingly, during an early phase (as early as 3 days postinfection) with low parasitemia, before the establishment of T cell unresponsiveness, a broad array of cytokine expression including IL-2 and IFN-gamma expression as well as marked lymphoproliferative response upon T cell mitogen- and TCR-mediated stimulation was observed. When the expression of cytokine gene in freshly isolated (ex vivo) splenocytes from P. yoelii-infected animals was investigated, a similar pattern of cytokine profile was detected. We devised a methodology in which RNA from an increasing number of splenocytes (ranging from 1 to 16 million) was used to compensate for any difference in the frequency of splenic T cells between immune and acutely infected mice and to augment target molecules which could be measured simultaneously by PCR. The data presented in this study led us to speculate that "anergy" or relative increase of a non-T cell population cannot account solely for the T cell unresponsiveness in the acute phase of infection. We suggest that inactivation or/and ablation of reactive T cells may explain T cell hyporesponsiveness during acute malaria.
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PMID:Plasmodium yoelii in mice: differential induction of cytokine gene expression during hyporesponsiveness induction and restimulation. 784 88

Using animal models or healthy volunteers, injection of lipopolysaccharide (LPS) or bacteria causes activation of macrophages with excessive synthesis and secretion of proinflammatory cytokines. Although these models mimic the effects of LPS in the host, they may represent more of an experimental expression of endotoxemia than natural infection itself. Therefore, as an ex vivo model of sepsis, whole blood from 15 patients with severe sepsis and 20 control patients without infection was stimulated with LPS to study the kinetics of mRNA expression and release of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6. Stimulation of whole blood with 1 microgram/mL LPS resulted in a maximum increase of cytokine secretion in the control group, while a marked (P < .01) depression of TNF-alpha, IL-1 beta, and IL-6 release was observed in the septic group, which persisted up to 10 days after study enrollment. While IL-1 beta mRNA expression was similar in peripheral blood mononuclear cells (PBMCs) harvested from LPS-stimulated whole blood in septic and control patients, the half-life and consequently the expression of TNF-alpha and IL-6 mRNA were strongly reduced in the septic group. These data indicate a downregulatory mechanism of cytokine release in whole blood from patients with severe sepsis that occurs on different levels. Although excessive secretion of proinflammatory cytokines has been considered deleterious for the host, the reduced capacity of PBMCs in whole blood from septic patients to synthesize and secrete proinflammatory cytokines to an inflammatory stimulus may result in immunodeficiency, because these cytokines in low concentrations are involved in the upregulation of essential cellular and humoral immune functions.
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PMID:Downregulation of proinflammatory cytokine release in whole blood from septic patients. 785 64

Patients with head injury must overcome central as well as peripheral metabolic insults. In addition to specific tissue damage to the brain, a cellular biochemical cascade occurs that can negatively affect organ function, cause a systemic response to injury, and may cause secondary tissue injury. The metabolites involved in this cascade are numerous and complex. Cytokines are important cell-to-cell communication mediators during injury. It is speculated that cytokines, such as interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF), and interleukin 8 (IL-8), which are found in elevated amounts in both human and basic trials after head injury, play a role in the cellular cascade of injury. Some of the metabolic events produced by small doses of cytokine infusion in animals, as well as humans, include fever, neutrophilia, muscle breakdown, altered amino acid metabolism, depression of serum zinc levels, production of hepatic acute phase reactants, increased endothelial permeability, and expression of endothelial adhesion molecules. These are all known sequelae of severe head injury. Cytokines have also been implicated in organ failure. Infusion of cytokines in basic science trials revealed that organ functions of the gut, liver, and lung are negatively altered by high-dose cytokine infusion. Infusion of certain cytokines has been shown to cause death of brain cells, increase blood-brain barrier permeability, and cause cerebral edema. This suggests that cytokines may also play a role in the sequelae of organ demise. These effects of cytokines have been attenuated in basic trials by blocking the initial signaling system of cytokines or by decreasing serum cytokine activity. We hypothesize that cytokines that are elevated after head injury play a role in the pathology of injury, including altered metabolism and organ demise.
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PMID:Cytokines and metabolic dysfunction after severe head injury. 786 40


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