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)

The in vivo effects of recombinant human interleukin 6 (IL-6) on the hematopoietic system of sublethally (4.8 Gy) x-irradiated mice were investigated. Animals were injected twice daily s.c. with IL-6 (10 micrograms/kg body weight/day) for 7 days following irradiation, and the numbers of hematopoietic stem, progenitor, and circulating blood cells were evaluated at 4, 7, 13, and 23 days. IL-6 caused significant depression of early hematopoiesis (decreased numbers of spleen colony-forming units [CFU-S] and granulocyte-macrophage colony-forming cells [GM-CFC]) in the spleens of irradiated mice. Marrow hematopoiesis was less affected by IL-6 injection, although the number of hematopoietic cells was also significantly lower than in irradiated mice injected with carrier alone. The observed decrease in the numbers of hematopoietic cells was not reflected by any significant change in the circulating blood cell numbers, which were similar to those in control irradiated animals. In contrast, IL-6 administered in 100 times higher doses (1000 micrograms/kg/day) caused significant increases in bone marrow and spleen cellularity and GM-CFC numbers, thus accelerating postirradiation hematopoietic regeneration. Our studies show that IL-6, administered in relatively low doses, suppresses postirradiation hematopoietic recovery, decreasing the numbers of stem and progenitor cells in sublethally irradiated mice.
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PMID:In vivo administration of interleukin 6 delays hematopoietic regeneration in sublethally irradiated mice. 162 4

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

Burned individuals display a reduced ability to elicit cellular and humoral immune responses and a depression in the vitro production of certain T-cell lymphokines. Treatment of burned mice with 100 micrograms of dehydroepiandrosterone within 1 hour after injury resulted in preserving a completely normal capacity to produce T-cell-derived lymphokines and to generate cellular immune responses. In addition, dehydroepiandrosterone-treated thermally injured mice demonstrated an above-normal ability to resist an induced infection with the intracellular pathogen, Listeria monocytogenes. Dehydroepiandrosterone-treated animals also did not exhibit the sustained plasma levels of interleukin 6 that normally accompany thermal injury and infection. Because of its antiglucocorticoid effects and positive immunoregulatory influences, we believe dehydroepiandrosterone to be a beneficial form of therapy for thermally injured individuals.
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PMID:Administration of dehydroepiandrosterone to burned mice preserves normal immunologic competence. 844 90

In each of 4 horses, sterile synovitis was induced by intra-articular injection of 3 micrograms of Escherichia coli endotoxin (lipopolysaccharide, LPS) into one antebrachiocarpal joint; an equal volume (2 ml) of phosphate-buffered saline solution (PBSS) was injected into the opposite, control carpus. Blood and 1.5 ml of synovial fluid were obtained at postinjection hours (PIH) 0, 2, 4, 8, 12, 18, 42, 66, and 144. Synovial fluid sample collection was accomplished by use of an indwelling, intra-articular catheter through PIH 12, and by arthrocentesis subsequently. Joint fluid samples were analyzed for cell counts, protein concentration, cytologic variables, and tumor necrosis factor (TNF), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) values. Tumor necrosis factor and IL-6 activities and WBC count were also measured in blood. To monitor local inflammation, skin temperature of each carpus was imaged, using a thermographic scanner prior to each sample collection time. Horses had minimal systemic effects. Mean (+/- SEM) rectal temperature increased significantly to 39.02 +/- 0.15 C only at PIH 18 after intra-articular injection of LPS. One horse had signs of mild depression from PIH 7 to 18, but its vital signs did not change appreciably. Each horse had mild signs of discomfort in the LPS-injected limb from PIH 1 to 3 until PIH 8 to 10. Mean peak surface temperature of the LPS-injected carpi was significantly higher than that of control carpi from PIH 8 to 144 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intra-articularly administered endotoxin on clinical signs of disease and synovial fluid tumor necrosis factor, interleukin 6, and prostaglandin E2 values in horses. 849 39

Topical exposure of mice to the contact allergen oxazolone induces both 4 persistent antigen-specific down-regulation of subsequent lymph node cell (LNC) proliferative responses stimulated by the same chemical and a more transient depression of LNC proliferative responses provoked by exposure to unrelated chemical sensitizers: the latter being associated with antigenic competition in contact sensitivity. In this paper a relationship between reduced LNC proliferative activity and the secretion of interleukin 6 (IL-6) is described. Pretreatment of mice with oxazolone caused a persistent, dose-dependent inhibition of LNC proliferative activity and a parallel reduction of IL-6 secretion when mice were re-exposed, at a different site, to the same chemical. Consistent with dendritic cells (DC) being the major source of IL-6 within allergen-activated lymph nodes, depletion of Thy-lt T lymphocytes did not compromise production of this cytokine. Although in mice pretreated with oxazolone IL-6 secretion by cultured LNC was impaired markedly, the initial IL-6 content of freshly isolated LNC was apparently normal. These data suggest that the down-regulation of lymphocyte proliferative responses induced by exposure of mice to oxazolone, and the consequential impaired responsiveness, is associated with, and possibly secondary to, the reduced secretion by lymph node DC of IL-6, a cytokine that is a costimulator of T lymphocyte activation and the production of which correlates closely with the vigour of LNC proliferative activity.
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PMID:Antigen-induced unresponsiveness in contact sensitivity: association of depressed T lymphocyte proliferative responses with decreased interleukin 6 secretion. 879 56

We have previously suggested that colorectal liver metastases might produce 'toxins' that reduce both quality of life (QoL) and survival. In this study we assessed whether QoL in patients with such metastases was related to immune activation, as determined by increased serum levels of interleukin 6 (IL6), soluble tumour necrosis factor receptor 1 (sTNFr1), soluble interleukin 2 receptor alpha (sIL2r alpha) or the interferon-gamma marker neopterin. Serum IL6, sTNFr1, sIL2r alpha, neopterin, alkaline phosphatase and carcinoembryonic antigen levels, liver metastasis volume, and QoL (Hospital Anxiety and Depression [HAD] scale, Rotterdam Symptom Checklist [RSC], and Sickness Impact Profile [SIP]) were measured in 43 patients. There were significant positive correlations between serum sIL2r alpha and HAD depression score (r = 0.66, P = 0.0001), RSC physical symptom score (r = 0.46, P < 0.01), and SIP score (r = 0.47, P = 0.009). Multiple regression analysis suggested that serum sIL2r alpha level was a significant independent predictor of HAD depression score. Although survival was shorter (logrank test P < 0.05) where sIL2r alpha, sTNFr1 and IL6 levels were higher, the ability of sIL2r alpha to predict HAD depression score was independent of survival.
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PMID:Relation between depression and circulating immune products in patients with advanced colorectal cancer. 981 54

Fibroblast-mediated cytokine gene therapy has proven to be a promising strategy for restoring hematopoiesis following repeated chemotherapy. Interleukin 3 (IL-3) and interleukin 6 (IL-6) can synergistically promote the recovery of hematopoiesis following chemotherapy. In this investigation, combined use of fibroblast-mediated IL-3 and IL-6 gene therapy was tested for hematopoietic effects on mice with or without 5-fluorouracil administration. The results demonstrated that combined therapy with IL-3 gene-modified NIH3T3 cell (NIH3T3-IL-3) and IL-6 gene-modified fibroblast NIH3T3 cell (NIH3T3-IL-6) implantation achieves obvious stimulation of hematopoiesis in normal mice and accelerates recovery of hematopoiesis. In normal mice the quantities of platelets, neutrophils, and total white blood cells in peripheral blood increased significantly after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells. The numbers of colony-forming unit (CFU) granulocyte/macrophage (CFU-GM) and CFU megakaryocyte (CFU-MK) formed by stem cells in bone marrow was significantly higher after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells than after the implantation of NIH3T3-IL-3 alone, NIH3T3-IL-6 alone, or neomycin gene-modified NIH3T3 cells. In hematopoiesis-depressed mice induced by preinjection with 5-fluorouracil at the dose of 150 mg/kg before cell implantation, the platelets, neutrophils, and white blood cells showed accelerated recovery, and the numbers of CFU-GM and CFU-MK formed by bone marrow cells were also markedly higher after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells than in control groups. Our data show that combined use of fibroblast-mediated IL-3 and IL-6 gene therapy may be of clinical relevance for the recovery of hematopoietic depression for patients after chemotherapy.
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PMID:Effects of fibroblast-mediated interleukin 3 and interleukin 6 gene therapy on hematopoiesis in mice treated with 5-fluorouracil. 982 23

A number of studies documented that the heavy metals are not only toxic for the organisms but they may modulate immune responses. The immunomodulatory activity was proved in several in vivo and in vitro model systems. In the current study, immunomodulatory activities of lead and cadmium are presented. The viability of both lymphocytes and macrophages was affected by heavy metals in a dose- and time-dependent manner. In the case of lead, the depression of N-oxide production closely correlated with increased blast transformation of spleen cells induced by concanavalin A (ConA). On the contrary, cadmium suppressed the production of N-oxides but stimulated significantly the proliferation of spleen cells. The production of cytokines by lymphocytes and macrophages was dependent on the in vitro model used. Generally, the treatment of macrophages with lead results in disregulation of the production of proinflammatory cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha) and interleukin 6 (IL-6)] and preferential production of Th1 type of cytokines (IFN-gamma and IL-2). Cadmium seemed to trigger the Th2 cytokine regulatory pathway [interleukin 4 (IL-4), interleukin 10 (IL-10)]. The results suggest the metal-induced changes in immunoregulatory mechanism of host with potentially severe clinical consequences.
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PMID:The immunomodulatory effect(s) of lead and cadmium on the cells of immune system in vitro. 1069 59

We investigated inflammatory cytokine response in chronic depressed patients during abdominal surgery. Twenty-five major depressed patients (Group D) and twenty-five patients (Group C) as the control were studied. Plasma interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured before and at 15 min after induction of anesthesia, the end of surgery, 24 h and 3 days after the operation. Plasma IL-6 concentrations in Group D at the end of the operation and 24 h after surgery were significantly lower than those of Group C. The plasma IL-6 concentration (87.1+/-55.3 pg/ml) of patients scoring more than 18 points in the Hamilton depression-rating score at the end of the operation was significantly higher than 57.5+/-76.7 pg/ml of patients scoring less than 18 points. Plasma IL-8 concentration (6.1+/-3.2 pg/ml) in Group D at the end of the operation was significantly lower than 8.7+/-4.2 pg/ml of Group C. We conclude that plasma IL-6 and IL-8 response to surgical trauma is inhibited in chronic depressed patients. The IL-6 response to surgical trauma is depending on the clinical state of depression.
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PMID:Plasma inflammatory cytokine response to surgical trauma in chronic depressed patients. 1114 50

Existing studies of the relationship between depression and osteoporosis have been heterogeneous in their design and use of diagnostic instruments for depression, which might have contributed to the different results on the comorbidity of these two conditions. Nevertheless, these studies reveal a strong association between depression and osteoporosis. Endocrine factors such as depression-induced hypersecretion of corticotropin-releasing hormone and hypercortisolism, hypogonadism, growth hormone deficiency and increased concentration of circulating interleukin 6, might play a crucial role in the bone loss observed in subjects suffering from major depression.
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PMID:Depression: a major, unrecognized risk factor for osteoporosis? 1139 44


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