Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After bone marrow transplantation many T-lymphocyte functions, including the production of cytokines (CK), such as interleukin 2, are severely depressed for months. The monocyte-derived cytokines tumor necrosis factor alpha and interleukin 6 are molecules central to immune functions. Moreover, they may be involved in graft-versus-host disease and in graft-versus-leukemia reaction. Hence, we have studied the reappearance of these CKs after BMT by analyzing whole blood cultures stimulated in vitro with lipopolysaccharide for 6 hr, followed by testing for the secretion of TNF in the WEHI 164/actinomycin D cytotoxicity bioassay and for IL-6 in the 7 TD 1 proliferation assay. We performed sequential studies in 6 children who were transplanted for aplastic anemia or leukemia with allogeneic bone marrow. We found that the production of both CKs can be induced as early as 10-14 days post BMT at the very beginning of engraftment, indicating that the regenerating monocyte system is recovering rapidly after BMT. Depletion and neutralization experiments confirmed that monocytes are the cellular source of the LPS-induced CK secretion after BMT. Control levels were reached 3 to 4 weeks post BMT. When analyzing the endotoxin-induced CK production in a larger panel of BMT patients after complete reconstitution, we could not detect any impact of acute or chronic GvHD, or of allogeneic or autologous BMT, nor did treatment with cyclosporine A (CsA) show any suppressive effect. Thus, our data show that the CK production of the monocyte/macrophage lineage is quite resistant to factors that do influence other cell lineages of the immune system during BMT. The coincident appearance of monocyte-derived cytokines and of GvHD suggests a role for these cytokines in GvHD in man.
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PMID:Recovery of monocytes after bone marrow transplantation--rapid reappearance of tumor necrosis factor alpha and interleukin 6 production. 192 48

Soluble interleukin-2 receptors (sIL-2R) are elevated in various disorders involving the activation of T cells. We measured serial serum concentrations of sIL-2R in 30 patients receiving allogeneic BMT to evaluate the usefulness of sIL-2R as a parameter for acute GVHD. In the 17 patients who developed acute GVHD, the sIL-2R concentration rose significantly on day 3 following transplantation, preceding the occurrence of acute GVHD. This change was not seen in the 13 patients without acute GVHD. The serum concentration of sIL-2R decreased as the acute GVHD subsided. The peak concentration of serum sIL-2R correlated with the severity of the acute GVHD. Simultaneous measurement of tumor necrosis factor alpha (TNF alpha) showed a significant rise in patients with acute GVHD, that became evident earlier than the sIL-2R elevation. TNF alpha concentrations also decreased following treatment of the acute GVHD. However, significant rise in TNF alpha were also seen in the early phase of allogeneic BMT in patients who did not develop acute GVHD. Our data suggest that the serum concentrations of sIL-2R as well as TNF alpha might reflect the severity of acute GVHD, and that the serum sIL-2R concentration might be a sensitive and practical indicator for acute GVHD.
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PMID:Serum concentration of the soluble interleukin-2 receptor for monitoring acute graft-versus-host disease. 864 Jan 64

Acute pulmonary dysfunction remains a frequent and severe complication of hematopoietic stem cell transplantation (SCT). Almost half of the pulmonary insults that occur in this seating are noninfectious in origin and are referred to as idiopathic pneumonia syndrome (IPS). In this series of 3 patients, etanercept (Enbrel; Immunex, Seattle, WA), a soluble, dimeric tumor necrosis factor alpha-binding protein, was administered to 3 consecutive pediatric allogeneic BMT recipients with IPS. The administration of etanercept, in combination with standard immunosuppressive therapy, was well tolerated and associated with significant improvements in pulmonary dysfunction within the first week of therapy. These data suggest that etanercept may represent a safe, non-cross-reactive, therapeutic option for patients with IPS and that clinical trials studying etanercept for this indication are warranted.
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PMID:Etanercept (Enbrel) administration for idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. 1217 86