UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Iron influences host immunity, in part by affecting the function and migration patterns of T cell subpopulations. Removal of iron stores from the body by chelation decreases proliferation and differentiation of T cells, as shown in models of autoimmunity and pancreatic islet transplantation. We have examined the influence of iron chelation on rejection of vascularized heart allografts in rats. Two protocols were investigated: "treated" recipients received desferrithiocin (30 mg/kg/day) orally for 10 days beginning the day of transplantation; "pretreated" hosts received a similar dose of the drug for 10 days before engraftment. Graft survival increased from about 7 days in untreated animals to 14-16 days in both treatment groups (P < 0.001). Histological and immunoperoxidase studies of allografts at day 7 showed that iron chelation resulted in only a mild reduction in cell infiltration, but in a marked decrease in graft edema and interstitial hemorrhage and essentially complete suppression of mononuclear cell activation and cytokine production. Chelation therapy was also found to inhibit profoundly cytokine (TNF-alpha) production in rats treated with LPS, consistent with the effects observed in situ in the allografts. In vitro studies showed that pretreatment significantly inhibited the mixed lymphocyte reaction. Chelation also influenced migration of T lymphocyte subsets: treatment stimulated migration of CD4+ lymphocytes to peripheral lymph nodes; pretreatment strikingly and selectively increased CD8+ cell migration into parathymic lymph nodes draining the graft, with the opposite effect on nondraining node groups. We conclude that treatment with iron-chelating agents has several effects on host alloresponsiveness in a rat heart graft model secondary to inhibition of immune activation; these include prolongation of graft survival, inhibition of the mixed lymphocyte reaction (pretreatment), marked depression of cytokine production, and alteration in recirculation patterns of lymphocyte subpopulations.
...
PMID:Iron chelation suppresses mononuclear cell activation, modifies lymphocyte migration patterns, and prolongs rat cardiac allograft survival in rats. 824 21

The production of the cytokines IFN-gamma, IL-1-alpha, IL-2 and TNF-alpha was investigated in mitogen-stimulated, whole blood cell culture from 239 untreated patients with primary gynaecological carcinomas (breast, cervix, ovary, endometrium), and 191 healthy female controls. The cytokines were measured in the 4-day post-induction supernatants by a sensitive enzymoimmunological assay. In the blood cell cultures of all four groups of cancer patients, significantly lower values of IFN-gamma (P < or = 0.001), IL-2 (P < or = 0.01) and IL-1 alpha (P < or = 0.01) were found as compared to the controls, although lymphocyte and monocyte counts were almost identical. Grouping the tumour patients into different clinical stages we could show in the four groups of carcinomas a gradual depression of the cytokine production according to growing tumour burden.
...
PMID:Impaired cytokine production in whole blood cell cultures of patients with gynaecological carcinomas in different clinical stages. 831 18

Although plasma levels of tumor necrosis factor (TNF) are elevated and hepatocellular dysfunction occurs even in the early hyperdynamic stage of sepsis, the precise mechanism responsible for this dysfunction remains unknown. Although TNF at high doses produces circulatory failure, it is not known whether the dose of TNF that does not adversely affect hemodynamics alters hepatocellular function. To study this, recombinant murine TNF-alpha was infused intravenously (0.05 or 0.25 mg/kg) over 30 min in normal rats. At 1 and 4 h after infusion of TNF-alpha or an equivalent volume of saline, hepatocellular function [i.e., maximum velocity (Vmax) and Michaelis constant (Km)] was assessed using in vivo indocyanine green clearance without blood sampling. Additional parameters measured were as follows: cardiac output by dye dilution, hepatic microcirculation by laser Doppler flowmetry and colloidal carbon infusion, plasma TNF and interleukin-6 (IL-6) by cytokine-dependent cellular assays, and plasma glucose enzymatically. The results indicate that although infusion of 0.05 mg/kg TNF-alpha did not affect Vmax and Km, its infusion at 0.25 mg/kg produced a significant depression of hepatocellular function and markedly increased the synthesis and/or release of IL-6. TNF-alpha-induced hepatocellular dysfunction was not associated with any significant changes in hepatic microcirculation, plasma glucose, cardiac output, and other measured hemodynamic parameters. Thus hepatocellular dysfunction observed after TNF infusion may be due to the direct effect of this cytokine alone or in combination with IL-6.
...
PMID:Tumor necrosis factor-alpha produces hepatocellular dysfunction despite normal cardiac output and hepatic microcirculation. 820 42

The cytokine response to injury or trauma is of interest in terms of both its mediation of the acute phase response and its possible relation to the immunological depression observed after major surgery. In this study, the production of cytokines IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6 and the naturally occurring inhibitor of IL-1, IL-1Ra, have been investigated in infants and children undergoing Swenson's pull-through operation for Hirschsprung's disease. Samples of peripheral blood were taken before, during and after surgery for the measurement of cytokines. IL-1Ra levels increased significantly (P < 0.01) at 2 h after commencement of surgery, with maximal levels for individual patients being attained between 3 h and 5 h (range 7.6-67.9 ng/ml). The mean level of IL-1Ra was maximal (26.2 ng/ml) at 5 h and returned to baseline levels between 24 h and 72 h. There were no changes observed in the circulating levels of IL-1 beta in nine out of 11 patients following commencement of surgery. TNF-alpha levels did not increase in any of the patients studied. IL-6 levels increased significantly (P < 0.02) 3 h after commencement of surgery, reaching maximum concentrations at 24 h (range 20-670 pg/ml), with levels falling between 48 h and 72 h. This study demonstrates, in vivo, the independent induction of IL-1Ra without a concomitant increase of IL-1 beta levels after major surgery. It also shows that IL-1Ra is the earliest cytokine produced in response to surgical stress.
...
PMID:Early induction of IL-1 receptor antagonist (IL-1Ra) in infants and children undergoing surgery. 834 47

Spaceflight materially influences the immune mechanism of humans and animals. Effects resulting from missions of less than 1 month are examined. Effects from longer missions are discussed in the companion paper by Konstantinova et al. Most immunology studies have involved analyses of subjects and samples from subjects obtained after flight, with the data being compared with similar data obtained before flight. These studies have demonstrated that short-duration missions can result in a postflight depression in blast cell transformation, major changes in cytokine function, and alterations in the relative numbers of immune cell populations. In addition to these post- vs. preflight studies, some data have been produced in flight. However, these in vitro analyses have been less than satisfactory because of differences between in-flight and ground-control conditions. Recently, both the U.S. and Russian space programs have started collecting in-flight, in vivo, cell-mediated immunity data. These studies have confirmed that the human cell-mediated immune system is blunted during spaceflight.
...
PMID:Immune changes during short-duration missions. 837 Oct 49

The goal of our study was to assess whether the human immunodeficiency virus (HIV) coat protein gp120 induces functional alterations in astrocytes and microglia, known for their reactivity and involvement in most types of brain pathology. We hypothesized that gp120-induced anomalies in glial functions, if present, might be mediated by changes in the levels of intracellular messengers important for signal transduction, such as cAMP. Acute (10 min) exposure of cultured rat cortical astrocytes or microglia to 100 pM gp120 caused only a modest (50-60%), though statistically significant, elevation in cAMP levels, which was antagonized by the beta-adrenergic receptor antagonist propranolol. More importantly, the protein substantially depressed [by 30% (astrocytes) and 50% (microglia)] the large increase in cAMP induced by the beta-adrenergic agonist isoproterenol (10 nM), without affecting that induced by direct adenylate cyclase stimulation by forskolin. Qualitatively similar results were obtained using a glial fibrillary acidic protein (GFAP)-positive human glioma cell line. The depression of the beta-adrenergic response had functional consequences in both astrocytes and microglia. In astrocytes we studied the phosphorylation of the two major cytoskeletal proteins, vimentin and GFAP, which is normally stimulated by isoproterenol, and found that gp120 partially (40-50%) prevented such stimulation. In microglial cells, which are the major producers of inflammatory cytokines within the brain, gp120 partially antagonized the negative beta-adrenergic modulation of lipopolysaccharide (10 ng/ml)-induced production of tumor necrosis factor alpha. Our results suggest that, by interfering with the beta-adrenergic regulation of astrocytes and microglia, gp120 may alter astroglial "reactivity" and upset the delicate cytokine network responsible for the defense against viral and opportunistic infections.
...
PMID:Human immunodeficiency virus coat protein gp120 inhibits the beta-adrenergic regulation of astroglial and microglial functions. 838 71

Treatment of the cloned NK-cell line (NKB61A2) with the major psychoactive marijuana component, delta-9-tetrahydrocannabinol (THC), for 24 h suppressed IL-2-induced proliferation of these cells in the cytokine concentration range of 0.25-10 pM suggesting that the drug inhibits the functional activity of the high affinity IL-2R. The proliferation inhibitory effect of THC was accompanied by a decrease in the number of high and intermediate affinity IL-2 binding sites as measured by equilibrium binding studies. However, the expression of Tac protein on the surface of these cells was increased as determined by flow cytometry analysis. THC was also shown to decrease proliferation and the number of IL-2 binding sites of cells previously pulsed with IL-2 and then treated with the drug in the absence of IL-2. These results suggest that THC inhibits IL-2-induced proliferation by modulating the expression of high affinity IL-2 receptors (alpha/beta) required for cell activation and also suppresses the ongoing process of functional receptor expression and clonal expansion of cells previously activated by IL-2. Because the number of intermediate binding sites is decreased following drug treatment along with an increase in the expression of Tac protein (alpha chain), the lowering of high affinity sites possibly results from a drug-induced depression of beta chain expression.
...
PMID:delta-9-Tetrahydrocannabinol (THC) decreases the number of high and intermediate affinity IL-2 receptors of the IL-2 dependent cell line NKB61A2. 838 28

IL-6 is a cytokine synthesized by T cells and macrophages (M phi). It has pleiotropic effects on diverse cell types and is recognized for its "pro-inflammatory" properties. In mice, IL-4, IL-5, IL-6, and IL-10 are produced by Th-2 cells. Because IL-10 suppresses Th-1 clones, and IL-4 broadly deactivates M phi, experiments were carried out to investigate the in vitro effects of recombinant human IL-6 on cytokine activation of human M phi. Pretreatment with IL-6 induced a dose- and time-dependent suppression of IFN-gamma (1000 U/mL) and TNF-alpha (25 ng/mL) activation of M phi for the killing of L. amazonensis. At doses greater than 0.1 to 100 ng/mL, IL-6 inhibited IFN-gamma and TNF-alpha activation by 21 to 93% and 36 to 82%, respectively. IL-6 alone had no effect on M phi viability and intracellular L. amazonensis growth. Blockade of M phi activation was greatest when IL-6 was added 24 or 48 h before infection and treatment with IFN-gamma or TNF-alpha. Furthermore, mAb against IL-6 abrogated the inhibitory activity of IL-6. Similarly IL-6 pretreatment suppressed M phi activation for antileishmanial capacity by IL-3, granulocyte-monocyte-CSF (GM-CSF) and IL-1 beta. Because cytokine induction of antileishmanial activity is associated with enhancement of oxidative capacity, the effect of IL-6 on this mechanism was evaluated. Pretreatment with IL-6 down-modulated TNF-alpha (25 ng/mL) enhancement of M phi oxidative capacity in a dose- and time-dependent manner. A similar depression of oxidative capacity was observed for GM-CSF and IL-3 but not for IFN-gamma. Furthermore, NG-monomethyl-L-arginine (a nitric oxide synthase inhibitor) had no effect on IFN-gamma and TNF-alpha activation of antileishmanial activity and nitrites/nitrates were not reliably assayed from M phi culture supernatants. These findings suggest that IL-6 down-modulates cytokine activation of M phi antileishmanial capacity by inhibiting oxygen-dependent and undefined oxygen-independent mechanisms.
...
PMID:IL-6 down-modulates the cytokine-enhanced antileishmanial activity in human macrophages. 839 59

Cultured aortic smooth muscle cells from spontaneously hypertensive rats produce more nitrite than cells from Wistar-Kyoto rats in response to interleukin-1 beta. Therefore, the effect of interleukin-1 beta-induced nitric oxide production was compared on the contractility of aortic smooth muscle from spontaneously hypertensive and Wistar-Kyoto rats. Under control conditions, there was no difference in the response of aortic rings (without endothelium) to phenylephrine between both strains. Contractions to 5-hydroxytryptamine were larger in preparations from hypertensive than normotensive animals. Treatment with interleukin-1 beta for 6 h reduced the responsiveness to both vasoconstrictors in a concentration-dependent manner. The depression was more pronounced in rings from spontaneously hypertensive rats: the threshold concentration of the cytokine was lower, and its maximal effect greater. Nitro-L-arginine prevented the inhibitory effect of interleukin-1 beta. The cytokine evoked a time-dependent loss of tone in phenylephrine-contracted rings with the same time of onset in both strains. However, the decay of tension was more pronounced in aortae from hypertensive than normotensive rats. In aortae from both strains, the decay was potentiated by L-arginine, but not D-arginine. Interleukin-1 beta elicited greater concentration-dependent productions of cyclic GMP and nitrite in rings from spontaneously hypertensive than from Wistar-Kyoto rats, and these were inhibited by methylene blue and nitro-L-arginine, respectively. The concentration-relaxation curves to 3-morpholino-sydnonimine were moderately, but significantly, shifted to the left in aortae from spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Enhanced production of nitric oxide in aortae from spontaneously hypertensive rats by interleukin-1 beta. 839 1

Haemorrhage in the absence of trauma is reported to induce a profound depression in cell-mediated immunity. Recent studies have drawn attention to the cytokine transforming growth factor-beta (TGF-beta) that, while important in wound healing, also has marked immunosuppressive effects. The aim of this study was to determine whether: (1) haemorrhage induces an increase in circulating TGF-beta and if this is associated with the loss of host immunoresponsiveness; and (2) administration of monoclonal antibody (mAb) to TGF-beta following haemorrhage ablates these changes. To determine this, C3H/HeN mice were bled to and maintained at a mean arterial pressure of 35 mmHg for 1 hr. This required removing approximately 50% of the circulating blood volume. Following this period of hypotension, the mice were adequately resuscitated. Blood samples obtained at 24 and 72 hr, but not at 2 hr, following haemorrhage showed a significant elevation in plasma TGF-beta levels when compared to shams. At 24 hr, the increase of TGF-beta in the plasma was associated with decreases in both concanavalin A (Con A)-induced splenocyte proliferation and splenic macrophage antigen presentation. Treating animals with neutralizing antibody (animals received 200 micrograms mAb against bovine TGF-beta 1,2,3/mouse intraarterially) not only reduced the levels of TGF-beta in the blood at 24 hr, but also restored splenocyte functions, such as Con A-induced proliferation, interleukin-2 (IL-2) release, and the capacity of splenic macrophages to present antigen. However, elevated levels of prostaglandin E2 (PGE2) seen in plasma during haemorrhage were only partially depressed by the antibody treatment. These results indicate that the release of TGF-beta contributes to the protracted (> or = 24 hr) suppression of cell-mediated immunity following haemorrhage.
...
PMID:The release of transforming growth factor-beta following haemorrhage: its role as a mediator of host immunosuppression. 840 75

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>