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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)

This paper reviews the role of the acute phase response and of cytokines in clinical bone marrow transplantation. Data are discussed from the literature and from the authors experience which show that measurement of C-reactive protein is a rather non-specific marker of tissue injury, but that it is elevated in graft-versus-host disease, and especially in infection. Cytokines are clearly implicated in several aspects of transplantation, and tumour necrosis factor in particular may be important. Although there are some data which associate high TNF levels with severe graft-versus-host disease, this association may not hold true in individual patients.
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PMID:Lymphokines and the acute-phase response in clinical bone marrow transplantation. 171 89

Acute graft-versus-host disease, interstitial pneumonitis, endothelial leakage syndrome, and veno-occlusive disease are major complications of bone marrow transplantation. Though several new regimens for prophylaxis and treatment of these syndromes have been introduced, the overall incidence has been only slightly reduced over the last few years. We retrospectively analyzed tumor necrosis factor alpha (TNF alpha) serum levels between day -8 and day 100 after bone marrow transplantation in 56 patients transplanted in our unit for a variety of hematological diseases. In 34 patients with uneventful courses, mean TNF alpha levels rose to a maximum of 76 +/- 29 pg/mL. In contrast, 22 patients with major transplant related complications showed mean increases of TNF alpha of 492 +/- 235 pg/mL (P less than .0001). Increases of TNF alpha occurred before interstitial pneumonitis and severe acute graft-versus-host disease with a latency of 25 to 54 days. Early complications such as endothelial leakage syndrome and veno-occlusive disease were closely associated with increases of TNF alpha serum levels. Our study suggests two pathways of TNF alpha release: activation of host macrophages and stimulation of donor cells in the course of acute graft-versus-host disease. Cytokine monitoring should be helpful for prediction and earlier treatment of major transplant related complications.
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PMID:Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. 226 57

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

Secretion of different cytokines may be an important T-cell effector mechanism for bone marrow engraftment, graft versus host disease and graft versus leukaemia effects after allogeneic bone marrow transplantation (BMT). Cytokine secretion and autocrine proliferative capacity of T-cell clones derived from leukaemia patients 3-6 weeks after allogeneic bone marrow transplantation were investigated. Only a minority of post-transplant T-cell clones (23/120; 19%) was capable of undergoing autocrine proliferation. By contrast, 21/65 (32%) normal control clones from the marrow donors derived under the same conditions were autocrine proliferative. All clones were interleukin-2 (IL-2) responsive. A majority (12/17; 71%) of autocrine proliferating post-transplant clones secreted detectable IL-2. Compared with control clones, CD4+ T-cell clones derived early after BMT produced decreased levels of interleukin-4 (IL-4) and interleukin-6 (IL-6), whereas secretion of interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) showed no significant difference. The small number (n = 8) of posttransplant CD8+ clones showed decreased production of IL-3, IL-4 and IL-6 compared with control clones, but normal secretion of GM-CSF. Neither CD4+ nor CD8+ T-cell clones secreted interleukin-7 (IL-7).
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PMID:Secretion of IL-2, IL-3, IL-4, IL-6 and GM-CSF by CD4+ and CD8+ TCR alpha beta+ T-cell clones derived early after allogeneic bone marrow transplantation. 832 61

The 4-1BB receptor is an inducible type I membrane protein and member of the tumor necrosis factor receptor (TNFR) superfamily that is rapidly expressed on the surface of CD4+ and CD8+ T cells after antigen- or mitogen-induced activation. Cross-linking of 4-1BB and the T cell receptor (TCR) on activated T cells has been shown to deliver a costimulatory signal to T cells. Here, we expand upon previously published studies by demonstrating that CD8+ T cells when compared with CD4+ T cells are preferentially responsive to both early activation events and proliferative signals provided via the TCR and 4-1BB. In comparison, CD28-mediated costimulatory signals appear to function in a reciprocal manner to those induced through 4-1BB costimulation. In vivo examination of the effects of anti-4-1BB monoclonal antibodies (mAbs) on antigen-induced T cell activation have shown that the administration of epitope-specific anti-4-1BB mAbs amplified the generation of H-2d-specific cytotoxic T cells in a murine model of acute graft versus host disease (GVHD) and enhanced the rapidity of cardiac allograft or skin transplant rejection in mice. Cytokine analysis of in vitro activated CD4+ and CD8+ T cells revealed that anti-4-1BB costimulation markedly enhanced interferon-gamma production by CD8+ T cells and that anti-4-1BB mediated proliferation of CD8+ T cells appears to be IL-2 independent. The results of these studies suggest that regulatory signals delivered by the 4-1BB receptor play an important role in the regulation of cytotoxic T cells in cellular immune responses to antigen.
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PMID:4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. 920 96

Cytokine-mobilized peripheral blood stem cell products are increasingly used for hematopoietic reconstitution after myeloablative therapy. Favorable engraftment kinetics, the ease of harvest, and the large number of CD34+ cells obtained that allow for graft manipulations (ie, tumor cell or T-cell depletion) have made this stem cell source an attractive alternative to marrow. More recent data suggest that in addition to the increased number of CD34 cells, there may be also qualitative differences between leukapheresis products and marrow. In the allogeneic transplantation setting, the one log more T cells contained in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells compared with marrow has not translated into more severe graft-versus-host disease, indicating possible differences in T-cell or accessory-cell function. Whether such differences will compromise graft-versus-leukemia effects and disease-free survival remains to be seen. Nevertheless, it is reasonable to speculate that cytokine-mobilized peripheral blood products may eventually replace marrow as a source for hematopoietic stem cells. However, each new mobilization strategy needs to be evaluated carefully, as comparable increases in CD34 cell numbers may not necessarily affect the same, as yet underlined, qualitative changes that make this product so attractive.
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PMID:Phenotype and engraftment potential of cytokine-mobilized peripheral blood mononuclear cells. 920 33

In the present study using an experimental BMT system we analyzed the effects of disparity at non-MHC Ag including minor lymphocyte stimulatory-1a (Mls-1a) Ag on the acute GVH reaction (GVHR) induced by MHC class I Ag. Mismatch at MHC (class I) Ag alone did not induce clinically detectable acute GVHR in this model. However, BMT mice prepared with a combination of both class I and non-MHC Ag mismatches showed signs of clinical GVHR and various cytokines were produced by the spleen cells at an early stage (4 days) after BMT. Although no clinical GVHR was detected in BMT chimeras prepared with a non-MHC mismatched but MHC matched combination, large amounts of various cytokines were secreted by spleen cells. Cytokine production in the latter two kinds of chimeras paralleled the increase of Mls-1a reactive Vbeta6+ T cells in the host spleen. Marked cytokine production induced by Mls-1a Ag was confirmed by MLR. Thus, these cytokines appeared to be produced by T cells responding to Mls-1a (ie Vbeta6+ T cells) and to augment the T cell responses to MHC class I which resulted in clinically detectable GVHR in chimeras prepared with the combination mismatched at both MHC class I and non-MHC loci.
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PMID:Effects of non-major histocompatibility antigens on acute graft-versus-host reaction after allogeneic bone marrow transplantation. 928 44

Serial cytokine and nitrate (as a measure of nitric oxide production) levels were assayed in nine consecutive patients undergoing allogeneic haemopoietic stem cell transplants. They were compared to those in 13 patients undergoing autologous transplants (transplant controls), 15 neutropenic patients with infective complications (patient controls) and 27 blood donors (normal controls). Peak nitrate, interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) levels were significantly higher in four allogeneic transplant patients with major non-infective complications compared to those without such complications, and control groups. Cytokine and nitrate levels peaked during conditioning therapy in the patients with veno-occlusive disease (one patient) and fulminant cholestatic liver failure (one patient), indicating that tissue damage may have been initiated during chemoradiotherapy in these patients, whereas peak levels occurred 2-3 days before graft rejection (one patient) and severe graft-versus-host disease (one patient), indicating a role for cytokine-induced nitric oxide release in the pathophysiology of these immune-mediated complications. Based on the data presented, it can be tentatively postulated that nitric oxide is a common proximate regulator of the immune response in host-versus-graft and graft-versus-host reactions.
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PMID:Cytokine-mediated nitric oxide release--a common cytotoxic pathway in host-versus-graft and graft-versus-host reactions? 933 54

Cytokine treatment is used increasingly for granulocyte and stem cell collection from healthy donors. This manuscript reviews the current literature on recombinant human granulocyte colony-stimulating factor (rhG-CSF)-induced expansion of circulating leukocytes, lymphocyte subsets, monocytes and granulocytes. There is a particular focus on the mobilization and peripheralization of stem cells, including quantitative and and kinetic aspects, the clonogenic potential of mobilized stem cells, and the rhG-CSF dose dependency of mobilization efficiency, RhG-CSF given to healthy individuals also affects the cytokine profile of mobilized and collected T cells, which after allotransplantation, might positively affect the incidence and severity of GVHD. Short- and long-term side-effects of rhG-CSF given to healthy individuals are discussed together with a consensus reached on safety considerations for healthy blood stem cell donors.
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PMID:Effects of granulocyte colony-stimulating factor in healthy subjects. 966 62

Cytokine-mobilized peripheral blood stem cells (PBSCs) are increasingly viewed as a promising alternative to bone marrow (BM)-derived stem cells for allografting in patients with hematologic malignancies. Preliminary results seem to indicate several potential advantages of this approach, such as: A) a more "donor-friendly" and possibly safer stem cell collection procedure; B) the procurement of a significantly larger number of progenitor cells (allowing for graft engineering opportunities); C) a faster hematopoietic engraftment including immunologic reconstitution, and D) comparable rates of acute graft-versus-host disease. Although the superiority of this approach over the traditional BM allografting has not been clearly demonstrated thus far in a randomized trial and many open issues remain, experience is accumulating rapidly, and major transplant centers worldwide seem to have endorsed this procedure. The acceptance of the peripheral blood as the primary source of stem cells for hematopoietic reconstitution in the allogeneic setting is likely to have a profound impact in areas such as graft-versus-leukemia/tumor effect, unrelated donor registries, and transplants. In the following, currently available information on blood stem cell harvesting and allografting is reviewed with the particular focus on donor safety.
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PMID:Peripheral Blood Stem Cells: A Novel Source for Allogeneic Transplantation. 1038 37


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