Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pteridine neopterin is a marker of immunological activation and has been shown to be a useful marker of graft-versus-host disease (GVHD) in bone marrow transplant patients. High levels of both neopterin and interferon-gamma (IFN-gamma) were produced in vitro during mixed lymphocyte responses, which may be considered to be a model of the primary events leading to GVHD. Neopterin was shown to be produced by monocytes in response to stimulation with IFN-gamma, but not other cytokines. However, the interleukins IL-1 alpha, IL-1 beta, IL-2, and tumour necrosis factor (TNF) alpha and beta, but not IL-6, stimulated neopterin production by unfractionated peripheral blood mononuclear cells (PBMC), and culture supernatants from PBMC stimulated with IL-1 alpha, IL-1 beta, IL-2 and IL-6, but not TNF-alpha or TNF-beta induced neopterin production following transfer to fresh monocyte cultures. It therefore appears that cytokines may generate neopterin by induction of IFN-gamma, by synergy with low levels of induced IFN-gamma, or by non-IFN-gamma-dependent mechanisms.
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PMID:Cytokine induction of neopterin production. 182 41

Highly purified and cloned preparations of interleukin-1 (IL-1) were found to antagonize the capacity of erythropoietin (Epo) to stimulate the proliferation of mouse spleen and bone marrow erythroid precursor cells (EPC) in culture. Cloned murine IL-1 and purified and cloned human IL-1 alpha and IL-1 beta were approximately equipotent in this assay. IL-1 inhibited the proliferation response of EPC even when added as long as 17 h after Epo, suggesting that IL-1 does not affect binding of Epo to receptors or biochemical events following shortly thereafter. Indomethacin did not influence the inhibitory effect of IL-1 on Epo-induced proliferation, and PGE2 had no demonstrable effect on the process. Tumor-necrosis factor-alpha and interferons beta 1, and gamma did not affect Epo-induced proliferation. It is suggested that IL-1 mediated antagonism of the effects of Epo on erythroid precursors is a factor in the pathogenesis of many types of hypoplastic anaemia, including those associated with infections, rheumatoid arthritis and systemic lupus erythematosus, giant-cell arteritis, graft-versus-host disease and disorders associated with lymphocyte-mediated suppression of erythropoiesis.
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PMID:Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. 349 70

Graft-versus-host disease (GVHD) is one of the major complications which should be resolved to improve the survival rates in allogeneic bone marrow transplantation (BMT). Recently, several cytokines have been identified, suggesting that they form a cytokine network and play an important role in immune system and hematopoiesis. Among several cytokines, it has been reported that tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are mainly involved in GVHD. In the present report, we analyzed the role of cytokines in GVHD. When we measured serum cytokine levels, IL-6, interferon gamma (IFN gamma), and TNF alpha levels were increased prior to the onset of acute GVHD. For chronic GVHD, a similar pattern of cytokine increment was observed. Interestingly, these cytokines appeared to interact synergistically to induce clinical GVHD, suggesting that none of those cytokines does not function solely. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that increased IL-1 beta mRNA expression was also observed in acute GVHD in addition to increased IL-6 and TNF alpha mRNA expressions. Unexpectedly, no increased IL-2 levels were observed in both assays. In hyperacute GVHD, only IL-6 level was increased. However, in vivo administration of IL-6 into allogeneic bone marrow chimeras did not induce severe GVHD. Therefore, some other factors also appeared to be involved in inducing hyperacute GVHD. Furthermore, it is important to consider the role of inhibitory cytokines such as transforming growth factor beta (TGF beta) or IL-10.
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PMID:Cytokines involved in graft-versus-host disease. 770 47

TNF alpha levels were determined by ELISA in serum from 112 BMT patients during pre-transplant conditioning. Patients who developed post-transplant complications had significantly higher TNF alpha levels than those without complications (mean 620 pg/ml vs 440 pg/ml, P = 0.04). In particular this effect is associated with patients who developed grade II-IV acute GVHD (mean 960 pg/ml, P < 0.001) and chronic GVHD (mean 724 pg/ml, P = 0.001). High TNF alpha levels were the only statistically significant risk factor for acute GVHD. IL-1 beta and IL-6 levels were not correlated with TNF alpha levels or posttransplantation complications. In multivariate analysis of chronic GVHD, patient age > 17 years and CMV disease were the only statistically significant risk factors. Relapse was associated with low levels of TNF alpha during conditioning (mean 318 pg/ml, P = 0.02). In multivariate analysis, high risk disease was the only factor that correlated with relapse. Low risk patients had significantly higher levels than high risk patients (551 vs 377, P= 0.04). CML and MDS patients had higher TNF alpha levels than acute leukemia patients. There was no difference in TNF alpha levels between patients conditioned with BU/CY and CY/TBI. We conclude that determination of TNF alpha levels during conditioning may be useful in the prediction of acute GVHD.
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PMID:TNF alpha levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD. 774 64

Cytokines play a key role in the pathogenesis of chronic Graft versus Host Disease (cGVHD) and various studies have shown abberant production of cytokines by immune cells from GVHD patients. Based on these findings and others showing that high TNF levels precede the development of GVHD, we evaluated inflammatory cytokine levels following BMT and during the development of cGVHD. In this study, patients undergoing bone marrow transplantation (BMT) who consequently developed chronic GVHD were analyzed as to their cytokine production during cGVHD and this was correlated with their clinical manifestations. A positive correlation was found between the severity as well as the number of major clinical complications and high levels of inflammatory cytokines (IL-1 beta IL-6 and TNF alpha) compared to control patients or to normal donors. Patients undergoing BMT who did not develop GVHD, did not produce high levels of IL-1 beta IL-6 or TNF. High levels of cytokines may be used as a tool for assessing novel therapeutic modalities and response to GVHD treatment.
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PMID:Cytokine dysregulation in chronic graft versus host disease. 777 55

Cytokines produced by T lymphocytes, monocytes/macrophages, and fibroblasts play a central role in the immune response and in the development of graft-versus-host disease (GVHD). Also, it has been reported that dysregulated production of cytokines maybe the primary mediator of clinical manifestation of acute GVHD. Regarding cytokine gene expression after human allogeneic bone marrow transplantation (allo BMT), we have demonstrated increased IL-1 beta, IL-6, and TNF-alpha mRNA expression in peripheral blood mononuclear cells during the development of acute and chronic GVHD and that the degree of the increase was dependent on the severity of the disease. Furthermore, overexpression of these cytokine mRNAs could be detected before the clinical manifestations of GVHD developed. In contrast, IL-2 mRNA expression was not detected in peripheral blood mononuclear cells in GVHD patients. On the other hand, we have reported that increased mRNA expression and protein product of IL-2 and IFN-gamma were evident in the mixed lymphocyte culture of the cases who developed severe lethal transplantation-related complications. Therefore, the detection of increased IL-2 and IFN-gamma gene expression in MLC appeared to be useful for predicting transplantation-related complications in BMT patients. Furthermore, we found increased IL-2 receptor alpha subunit mRNA expression in the peripheral blood mononuclear cells during GVHD. These findings may indicate the important role of inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha in the development of the clinical manifestation of GVHD and also may be indicative of the important role of IL-2 and the IL-2 receptor in allo response perhaps mainly as an autocrine effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine gene expression after allogeneic bone marrow transplantation. 778 51

Interleukin-1 (IL-1) molecules are cytokines involved in the acute-phase response against infection and injury. Three naturally occurring IL-1 molecules are known, two agonists: IL-1 alpha and IL-1 beta, and one antagonist, the IL-1 receptor antagonist (IL-1ra). Although IL-1 action protects the organism by enhancing the response to pathogens, its overproduction can lead to pathology and has been implicated in disease states that include septic shock, rheumatoid arthritis, graft versus host disease and certain leukemias. The crystal structure of IL-1ra has been solved at 0.21-nm resolution by molecular replacement using the IL-1 beta structure as a search model. The crystals contain two independent IL-1ra molecules which are very similar. IL-1ra has the same fold as IL-1 alpha and IL-1 beta. The fold consists of twelve beta-strands which form a six-stranded beta-barrel, closed on one side by three beta-hairpin loops. Cys69 and Cys116 are linked via a disulfide bond and Pro53 has been built in the cis-conformation. Comparison of the IL-1ra structure with the IL-1 alpha and IL-1 beta structures present in the Protein Data Bank shows that a putative receptor interaction region, involving the N-terminus up to the beginning of strand beta 1 and the loops D and G, is very different in the three IL-1 molecules. Other putative interaction regions, as identified with mutagenesis studies, are structurally conserved and rigid, allowing precise and specific interactions with the IL-1 receptor.
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PMID:Refined crystal structure of the interleukin-1 receptor antagonist. Presence of a disulfide link and a cis-proline. 786 45

To determine the degree of graft versus host disease (GVHD) prophylaxis that might be necessary if cord blood (CB) transplantation is more widely applied, we compared human cord blood mononuclear cell (CBMC) and adult peripheral blood mononuclear cell (PBMC) proliferative responses and stimulatory capabilities; to examine the utility of UVB irradiation for GVHD prophylaxis, we compared proliferative responses, antigen-presenting cell (APC) stimulatory functions, and cytokine production by untreated and UVB-irradiated CBMCs. The two cell types, CBMC and PBMC, proliferated equally both in response to phytohemagglutinin (PHA) and alloantigen in mixed lymphocyte culture (MLC). Cord blood stimulatory function in MLC was significantly (P < 0.05) reduced to 60% of PBMC stimulatory capability. Ultraviolet-B irradiation at a dose of 100 J/m2 of CBMCs significantly (P < 0.01) inhibited PHA stimulation by 79.4%, reduced responder activity in MLC by 75.8%, and inhibited stimulatory activity in MLC by 55.6% as compared with the activity shown by untreated CBMCs. The same dose of UVB preserved 59.9% of CFU-GM and 65.9% of BFU-E colony growth as compared with untreated CBMCs. Production of lymphokines (IL-2, GM-CSF, LIF, and gamma-IFN) by PHA-stimulated CBMCs was decreased, but monokine (IL-1 beta and IL-6) production was unchanged. We conclude that UVB irradiation at a dose of 100 J/m2 inhibits CB lymphocyte activation and preserves the cellular growth potential of CB hematopoietic progenitor cells.
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PMID:The effect of UVB irradiation on proliferative activity and cell growth potential of cord blood. 807 20

Cytokine gene expression in peripheral blood mononuclear cells during the development of graft-versus-host disease (GVHD) in patients who underwent allogeneic bone marrow transplantation (allo BMT) was analysed using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of interleukin (IL)-1 beta, IL-6, and tumour necrosis factor (TNF)-alpha mRNA was increased during the development of GVHD and the degree of this increment depended on the severity of the disease. IL-2 expression was not detected at all and interferon-gamma expression was not much changed during GVHD. In patients with hepatic veno-occlusive disease (VOD), another transplantation-related complication, the expression of IL-1 beta and TNF-alpha mRNA was increased but IL-6 mRNA expression showed little increase. These findings suggest that IL-1 beta, IL-6 and TNF-alpha produced by peripheral blood mononuclear cells play an important role in the development of GVHD. Furthermore, liver dysfunction due to GVHD or VOD may be distinguishable by this type of cytokine analysis. Analysis of cytokine mRNA expression in peripheral blood mononuclear cells after allogeneic bone marrow transplantation may provide important information concerning the immune response and the cytokine network system in marrow transplant patients.
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PMID:Cytokine gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation. 813 79

Plasma concentrations and peripheral blood cells containing cytoplasmic cytokines were monitored during the post-transplant period in 10 patients who had received allogeneic bone marrow transplants (BMT) for the correction of inherited genetic disorders. The presence of CD14-positive cells containing cytoplasmic interleukin-1 alpha and beta in the peripheral blood was indicative of acute graft-versus-host disease (GVHD). Plasma concentrations of IL-1 alpha, IL-1 beta and TNF-alpha were significantly raised in the GVHD group when compared with the uneventful days. There was, however, poor temporal correlation between the plasma concentrations and clinical manifestations of acute GVHD. Cells containing cytoplasmic IL-6 were present in the peripheral blood when patients had clinically suspected and/or microbiologically confirmed infection. The results from this study demonstrate that analysis of peripheral blood cells for cytoplasmic IL-1 alpha and IL-1 beta are better markers of acute GVHD than is monitoring plasma concentrations of these cytokines.
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PMID:Monitoring cytokine production in peripheral blood during acute graft-versus-host disease following allogeneic bone marrow transplantation. 813 47


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