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

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.
 ...
PMID:Cytokines involved in graft-versus-host disease. 770 47

To assess the influence of pretransplant cytoreductive therapy with special reference to interferon-alpha (IFN-alpha) treatment on major endpoints of allogeneic bone marrow transplantation (BMT), we studied 133 consecutive patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in first chronic phase who received marrow grafts from HLA-identical family (n = 103) or alternative donors (n = 30) at a referral-based transplant center. Fifty of these patients (38%) were previously exposed to IFN-alpha for a median duration of 14 months (range, 1 to 61 months), whereas 83 patients (62%) exclusively received hydroxyurea and/or busulfan therapy between 1 and 129 months (median, 15 months) pretransplant. Using the categorized treatment duration with each pretransplant cytoreductive agent as a measure for individual patient exposure to each agent, prolonged ( > 12 months) IFN-alpha administration was identified as the sole significant pretransplant therapy-related predictor of transplant outcome by proportional hazards regression analysis. The adjusted risk ratio (RR) of transplant-related mortality (TRM) was 2.5-fold higher (95% confidence limits [95% CL], 1.4 to 4.5; P < .004) compared with other pretransplant therapy and this was mainly attributable to a 3.1-fold higher RR (95% CL, 1.4 to 6.4; P < .005) of fatal posttransplant infections after prolonged IFN-alpha treatment pretransplant. Marrow graft failure developed exclusively among 7 of 30 patients (23%) with donors other than HLA-identical family members and was further restricted to patients who had been previously exposed to IFN-alpha. The probability of graft failure was 49% +/- 28% in 17 patients pretreated with IFN-alpha compared with 0% for the other 13 patients with mismatched family or unrelated donors (P < .008). In addition, a significant delay in neutrophil and platelet count reconstitution was observed among patients with donors other than HLA-identical family members after pretransplant IFN-alpha exposure. No influence of pretransplant cytoreductive therapy on either acute and chronic graft-versus-host disease or leukemic relapse was detected in this study. As a consequence of its adverse effect on TRM, prolonged pretransplant IFN-alpha treatment was independently associated with a 2.5-fold lower likelihood (95% CL, 1.4 to 4.5; P < .003) of 5-year overall survival and with a 2.3-fold lower likelihood (95% CL, 1.3 to 4.2; P < .004) of 5-year disease-free survival postransplant after adjustment for other significant prognostic factors in multivariate analysis.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Prolonged administration of interferon-alpha in patients with chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia before allogeneic bone marrow transplantation may adversely affect transplant outcome. 774 58

Cord blood has been used successfully for stem cell transplantation in several haematological conditions: Fanconi's anaemia, leukaemia and Wiskott-Aldrich syndrome. On account of the low incidence of GVHD observed following cord blood transplantation, it has been suggested that cord blood be used for HLA-matched, or perhaps one or two antigens mismatched, and unrelated stem cell transplantation. Based on an extensive immunophenotype-functional correlation, we determined that cord blood contains mainly immature unprimed T lymphocytes that are predominantly suppressor cells. Recent findings suggest that dysregulated production of cytokines (IL-1, IL-2, TNF alpha) plays a role in GVHD. We showed that T cells in cord blood express receptors for IL-2, TNF alpha, but no receptors for IL-1. Similarly, NK cells, one of the effector cells of GVHD, express receptors for TNF alpha and gamma IFN but do not express receptors for IL-1, nor IL-2R alpha-chain (CD25) although IL-2R beta-chain is expressed. The potential for activation of T lymphocytes and NK cells therefore exists in the context of bone marrow transplantation. However, the high number of suppressor cells in cord blood most likely modulate the activation of lymphocytes and NK cells thereby minimizing GVHD.
 ...
PMID:Phenotypic analysis of functional T-lymphocyte subtypes and natural killer cells in human cord blood: relevance to umbilical cord blood transplantation. 777 9

Keratinocytes are activated to express MHC class II and ICAM-1 molecules during cutaneous inflammatory reactions. It is controversial how the interaction between these 'nonprofessional' antigen presenting cells (APC) and infiltrating T cells affects the local inflammatory response. To address this issue we analyzed whether IFN gamma-treated cultured human keratinocytes would activate established Th cell clones in vitro. Three allo DR specific T cell clones were induced to proliferate in a HLA-DR and LFA-1/ICAM-1 dependent fashion upon coculture with intact layers of IFN gamma stimulated keratinocytes. Likewise, keratinocytes also could activate two out of four minor histocompatibility (mH) antigen specific Th cell clones obtained from peripheral blood leukocytes (PBL) of graft versus host disease patients. The T cell activating potential of MHC class II+ keratinocytes was shown to be relatively low compared to specialized APC as PMNC and EBV-BLCL. Most strikingly, measurable allo MHC and mH antigen specific Th cell proliferation was only induced by using adherent keratinocytes at low cell densities, but not by keratinocytes in suspension. The results presented here indicate that in vitro conditions may crucially influence observations regarding the T cell activating potential of MHC class II expressing keratinocytes. Furthermore, our results indicate that, in addition to a tolerizing effect as suggested by previous reports, interaction of primed antigen specific T cells with activated keratinocytes may also result in enhancement of a cutaneous immune response in vivo.
 ...
PMID:Human keratinocytes activate primed major and minor histocompatibility antigen specific Th cells in vitro. 791 50

Hyperacute graft-versus-host disease (GVHD), which progresses severely and rapidly, was observed in three patients with acute leukemia transplanted with bone marrow cells from human leukocyte antigens (HLA)-identical and mixed leukocyte reactions (MLR)-negative siblings. Hyperacute GVHD developed in these patients within 7 days after bone marrow transplantation (BMT) and was rapidly aggravated inspite of cyclosporin A (CyA) and short-term methotrexate (MTX) prophylaxis and treatment with bolus methylprednisolone (mPSL). These patients showed markedly increased serum interleukin-6 (IL-6) levels after BMT, whereas other cytokines such as interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), and IL-2 were not increased compared with pretreatment levels. These findings suggest that markedly increased IL-6 levels may be related to hyperacute GVHD.
 ...
PMID:Hyperacute graft-versus-host disease accompanied by increased serum interleukin-6 levels. 791 41

In patients with acute graft-versus-host disease (GVHD), IL-6 gradually increased > 14 days before clinical onset of acute GVHD and decreased when acute GVHD disappeared. Interferon-gamma (IFN gamma) levels increased < 14 days before clinical acute GVHD and decreased at the disappearance of acute GVHD. Tumor necrosis factor-alpha (TNF alpha) levels increased almost simultaneously with the onset of acute GVHD and also decreased when it disappeared. However, these results do not necessarily mean that the increased levels of IL-6, IFN gamma and TNF alpha induced acute GVHD; they merely show that acute GVHD is observed more frequently in patients with increased IL-6, IFN gamma and TNF alpha levels than in those with normal levels. Although increased IL-6 levels were also observed in patients without acute GVHD, concomitant increase of IFN gamma and TNF alpha was not detected in such cases, showing that IL-6 can be increased by even graft-versus-host reaction (GVHR) which may not develop into clinical acute GVHD. Taken together, acute GVHD appeared to be induced by synergistic interaction of IL-6, IFN gamma and TNF alpha, consistent with a cytokine cascade. A similar interaction of IL-6 and TNF alpha was also observed in chronic GVHD. Although IFN gamma levels were slightly increased in chronic GVHD and sometimes aggravated the disease status, IL-6 and TNF alpha appeared to be more closely involved in the induction of chronic GVHD. In autologous BMT, increased cytokine levels were not observed unless IL-2 was administered.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum cytokine levels in bone marrow transplantation: synergistic interaction of interleukin-6, interferon-gamma, and tumor necrosis factor-alpha in graft-versus-host disease. 792 Mar 9

In a patient undergoing allogeneic BMT for chronic phase CML, de novo chronic GVHD developed within 80 days after transplantation. Eighteen months post-BMT, high serum levels of neutralizing interferon-alpha (IFN-alpha) antibodies were detected, which persisted despite continuous immunosuppressive treatment. The antibodies were of oligoclonal or polyclonal origin, predominantly of the IgG1 type, and reacted broadly with various human IFN-alpha types, including the patients endogenous IFN-alpha, but failed to recognize natural IFN-beta and recombinant IFN-gamma. Pathogenesis and clinical impact of the IFN-alpha antibodies are unknown. Antibodies of cytokines are a novel class of autoantibodies that may develop after allogeneic BMT and interfere with cytokine homeostasis and immune regulation.
 ...
PMID:High-titre interferon-alpha antibodies in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation. 799 79

An in vitro skin explant model has been used to predict the severity of acute graft-versus-host disease (GVHD) in 34 HLA-identical bone marrow transplant recipients (correlation coefficient 0.6 p < 0.001). Supernatants from HLA-matched patient/donor mixed lymphocyte cultures (MLCs) were analysed for levels of tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). High levels of both cytokines correlated with the development of GVHD grades II or above (p < 0.05). The supernatants were also tested for induction of class II MHC antigen expression on third party skin and results correlated with clinical outcome in 17 of 22 cases (77%) (correlation coefficient 0.65, p < 0.001). The results suggest that measurement of both TNF alpha and IFN gamma in HLA-matched MLC supernatants is of predictive value and that the skin explant model is a useful model for studying the aetiology of GVHD in humans.
 ...
PMID:Cytokine involvement in predicting clinical graft-versus-host disease in allogeneic bone marrow transplant recipients. 801 55

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.
 ...
PMID:The effect of UVB irradiation on proliferative activity and cell growth potential of cord blood. 807 20

A murine model of bone marrow (BM) transplantation in which donor (B10.D2) and recipient (BALB/c) mice were major histocompatibility complex (MHC) (H-2d) and Mls-1 identical, but incompatible at multiple non-MHC minor histocompatibility (H) antigens, and at Mls-2,3 was used to examine regeneration of B-cell development during the minor H antigen graft-versus-host reaction (GVHR). Mice that received T-cell-depleted allogeneic BM regained significant pre-B cells (sIg- 14.8+) in their BM. Mice undergoing GVHR after transplantation with allogeneic BM + T cells had less than 2% pre-B cells in their BM at day 7 and only 12% to 14% pre-B cells at days 21 and 28 compared with greater than 20% pre-B cells in the allogeneic controls. After partial recovery, the pre-B cells in the BM of GVH mice again decreased to less than 3% by day 42. This abnormal pattern of pre-B cell development in mice undergoing GVHR was associated with a reduced response to interleukin-7 (IL-7) in vitro. The delay in B-lineage cell reconstitution in mice with GVHR correlated with the expansion of donor V beta 3+ T cells in both the spleen and BM. BM T cells from mice with GVHR as well as isolated V beta 3+ T cells inhibited IL-7 colony-forming units from normal BM in co-culture assays. This inhibition could be reversed with anti-interferon gamma (IFN gamma) antibody. These data suggest that the delay in appearance and the reduction in proportion and number of pre-B cells observed early during the GVH reaction in this model is caused, in part, by the inhibitory actions of IFN gamma derived from donor V beta 3+ T cells on B-lineage cell development.
 ...
PMID:Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction. 821 28


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