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)

The present study was designed to determine whether .N = O produced in vivo during the rejection of histoincompatible tissues might permit serum NO2-/NO3- levels to serve as markers of a rejection reaction. Rat syngeneic and allogeneic liver, heart, bone marrow/spleen cell, small bowel, skin, and sponge matrix grafts were performed and the stable end-products of .N = O, NO2-/NO3-, were serially assayed in the serum of the grafted animals. A significant rise of serum NO2-/NO3- levels in the allografted animals preceded the onset of clinical signs of rejection or graft-versus-host disease, with the exception of the skin and sponge matrix graft models, where elevated serum NO2-/NO3- levels were never observed. In all transplant models, normal serum NO2-/NO3- levels were observed at all times in animals that received syngeneic grafts. Furthermore, treatment of allograft recipients with the immunosuppressive agents FK 506 or cyclosporine A inhibited .N = O production. Determination of serum creatinine levels demonstrated that the elevated serum NO2-/NO3- levels were not caused by kidney dysfunction. Serum NO2-/NO3- levels might be useful early serum markers of the initiation of a rejection reaction or graft-versus-host disease when functional markers of graft dysfunction are not apparent.
 ...
PMID:Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat. 137 17

Due to the accumulation of evidence concerning a putative role of nitric oxide (NO) in graft-versus-host disease (GVHD), we performed follow-up measurements of the stable end-products of NO, nitrite/nitrate (NO2-/NO3-) in plasma of patients undergoing allogeneic (n = 16) and autologous (n = 6, as a control) bone marrow transplantation. NO2-/NO3- concentrations were set in relation to the clinical course and to serum levels of soluble tumor necrosis factor receptor 75 (sT-NFrec 75) and neopterin, both of which are known to be sensitive indicators of cellular immune activation phenomena involving macrophages in vivo, and endogenous interleukin (IL)-10, a major T helper cell type 2 (TH-2)-derived cytokine and potent inhibitor of macrophage activation and NO formation. A significant rise of NO2-/NO3- levels was observed in patients with GVHD and preceded the onset of clinical symptoms by up to 3 days. In contrast to indicators of macrophage activation, i.e., neopterin and sT-NFrec75, NO2-/NO3- concentrations were not significantly altered from baseline levels during infectious complications, as NO2-/NO3- concentrations did not fluctuate in patients after autologous engraftment. During episodes of acute GVHD, NO2-/NO3- concentrations showed a strong positive correlation with levels of plasma neopterin and sTNFrec 75, but were also significantly related to IL-10. In non-GVHD patients, a negative correlation between IL-10 and NO2-/NO3- concentrations was evident. Therefore, NO2-/NO3- determination may be a valuable early indicator of the initiation of human GVHD. Our results provide some further insights concerning cytokine-related metabolic changes in the course of human GVHD in vivo which may prove useful in the development of new therapeutic approaches for this disease.
 ...
PMID:Nitric oxide formation as predictive parameter for acute graft-versus-host disease after human allogeneic bone marrow transplantation. 852 17

The suppressed lymphocyte proliferative responses characteristic of graft-versus-host disease (GVHD) are due, in part, to production of nitric oxide (NO). In order to more fully elucidate the role of NO during GVHD, an NO synthesis inhibitor, aminoguanidine (AG), was administered to unirradiated (C57BL/6J X DBA/2J)F1 mice injected with 5 X 10(7) C57BL/6J splenocytes. Administration of AG resulTed in abrogation of the elevation in serum NO2- + NO3- levels characteristic of GVHD. A significantly increased percentage of splenocytes of host phenotype (H2b/d, B220+, and THY1.2+) and a significantly higher hematocrit value were detected in GVHD animals receiving AG therapy. Additionally, the Con A-induced proliferative response of splenocytes obtained from GVHD mice receiving AG therapy was increased compared with the responses of splenocytes from animals that did not receive AG therapy. Parameters not affected by AG therapy included NO synthesis by recovered peritoneal macrophages, donor antihost cytolytic activity in splenocyte populations, serum GM-CSF levels and long-term engraftment of donor cells. These data indicate that NO may play a role in the destruction of both lymphoid and erythroid host tissue as well as the reduced lymphoproliferative responses associated with the acute phase of GVHD.
 ...
PMID:Bystander injury of host lymphoid tissue during murine graft-verus-host disease is mediated by nitric oxide. 861 Mar 89

We have previously demonstrated that administration of the nitric oxide (NO) synthesis inhibitor aminoguanidine (AG) to mice undergoing nonlethal graft-versus-host disease (GVHD) results in less destruction of host tissue and enhanced proliferative responses of splenic lymphocytes. Subsequently, we have determined whether the amelioration of GVHD pathology associated with inhibition of NO synthesis affects survival in a lethal GVHD model. Utilizing a C57BL/6 to C57BL/6xDBA2JF1 model, administration of parental lymph node lymphocytes instead of splenocytes results in 80-90% lethality by week 4 after GVHD induction. Administration of AG resulted in significantly decreased lethality coincident with decreased serum NO2- + NO3- levels. AG therapy had no effect on donor anti-host cytolytic T cell activity, which indicates that destruction of host tissue via this pathway was unaffected by the therapy. Histological evaluation of spleen, small intestine, bone, and mesenteric lymph node did not reveal any difference in the histological correlates of disease in the treated mice. AG increased various hematopoietic indices, including red blood cell count, white blood cell count, and hemoglobin, which indicates that the disruption of hematopoiesis during acute GVHD is mediated in part by NO. In addition, the number of GVHD mice with endogenous bacterial infections in the spleen and liver was significantly decreased in mice receiving AG therapy. These data indicate that NO plays a detrimental role during GVHD that appears to result in decreased hematopoietic indices and concomitant susceptibility to bacterial infection.
 ...
PMID:Attenuation of lethal graft-versus-host disease by inhibition of nitric oxide synthase. 900 Jun 68