G-CSF

Granulocyte CSF was first identified (as CSF-/J) in placenta-conditioned medium and was shown to induce the differentiation of murine myelo- 

G-CSF may be related to IL-6 because both the number and size of in-trons and exons in these two genes are similar. Furthermore, amino acid residues 20-85 in G-CSF and 28-91 in IL-6 have 26% homology, and the positions of four cysteine residues in these regions are precisely conserved. Whilst the IL-6 gene is located on chromosome 7pl5, it may be that the two genes arose from duplication and have since diverged. 

G-CSF increases the number of progenitor cells in the bloodstream tenfold. It has been used in the treatment of patients with myelodysplastic syndromes (MDS 8.8) where it can increase neutrophil counts and sometimes improve neutrophil function in these patients. Because some leukaemic cells are able to proliferate rather than differentiate in response to G-CSF, this CSF may potentially induce a leukaemic transformation in these patients however, its combined use with cytotoxic agents such as cytosine arabinoside appears to decrease this possibility. No doubt clinical trials already underway will establish the optimal treatment regimen for G-CSF, so that the beneficial effects of this cytokine for the treatment and management of haematological disorders can be realised. 

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GM-CSF, G-CSF, M-CSF, multi-CSF cytotoxic injury bone marrow transplantation myelodysplastic syndromes AIDS neutropenia rodent and human... 

Similar results have been reported in sublethaHy and lethaHy irradiated dogs, where G-CSF reduced the severity and duration of neutropenia and the duration of thrombocytopenia (161). G-CSF increases the survival of lethaHy irradiated animals by inducing eadier recovery of neutrophils and platelets. GM-CSF also decreases the severity and duration of neutropenia in dogs exposed to 2.4 Gy (2400 rad) TBI, but does not influence monocyte or lymphocyte recovery (162), indicating its expected selective action. 

Clinically, GM-CSF or G-CSF have been used to accelerate recovery after chemotherapy and total body or extended field irradiation, situations that cause neutropenia and decreased platelets, and possibly lead to fatal septic infection or diffuse hemorrhage, respectively. G-CSF and GM-CSF reproducibly decrease the period of granulocytopenia, the number of infectious episodes, and the length of hospitalization in such patients (152), although it is not clear that dose escalation of the cytotoxic agent and increased cure rate can be rehably achieved. One aspect of the effects of G-CSF and GM-CSF is that these agents can activate mature cells to function more efficiently. This may, however, also lead to the production of cytokines, such as TNF- a, that have some toxic side effects. In general, both cytokines are reasonably well tolerated. The side effect profile of G-CSF is more favorable than that of GM-CSF. Medullary bone pain is the only common toxicity. 

Interleukin-1 OC and (3. IL-1 has radioprotective activity toward BM and other tissues (151,164). IL-1 is produced in response to endotoxin, other cytokines, and microbial and viral agents, primarily by monocytes and macrophages. Other nucleated cells can also produce it. IL-1 appears to play an important role in the regulation of normal hemopoiesis directly by stimulating the most primitive stem cells and indirectly by stimulating other hemopoietic factors, including G-CSF, GM-CSF, M-CSF, and IL-6. 

A critical step in radioprotection involves the IL-1 receptors. Monoclonal antibodies to the type 1 IL-1 receptor block IL-l-induced radioprotection (167). Although this receptor is not present on BM cells, it is present on fibroblasts, which suggests that the effects of IL-1 on stem cells maybe largely indirect and mediated by stromal cell activation (168). Anti-IL-1 receptor (type 1) also sensitizes normal mice to the effects of TBI, which suggests that endogenous IL-1 has an intrinsic radioprotective role. IL-6 induction by IL-1, but not CSF levels, is inhibited, which supports the concept that G-CSF and GM-CSF are insufficient by themselves at radioprotecting stem cells and indicates a contributory role for IL-6. Anti-IL-6 antibody blocks IL-1 and TNF-induced radioprotection and also decreases the intrinsic radioresistance of mice, as does anti-TNF- a (169). 

Electronegatively substituted acetylenes, such as dimethyl acetylenedicar-boxylate, do not react under normal conditions but will add the elements of hydrogen fluoride by reaction with fluoride ion (e g, CsF or tetraalkylammonium dihydrogen trifluoride) and a proton source under phase-transfer conditions [49, 50] (equation 8)... 

Cellular cytokines (interferons, G-CSF) and immune response modifiers originally produced from human cells, most often leukocytes, have now been replaced with recombinant products with well-defined structure/function. Futuristic advances in experimental hematology portend development of human blood cells produced from the hemopoetic stem cells. Yet for the foreseeable future, homologous blood donated by healthy, altruistic voluntary blood donors remains the principal source of safe and adequate supply of blood and blood products for transfusion therapy. 

G-CSF (recombinant products molgramostim, sar-gramostim) is locally active and remains at the site of infection to localize and activate neutrophils [4]. Like G-CSF, GM-CSF stimulates the proliferation,... 

SCF (recombinant product ancestim) is an early-acting hematopoietic growth factor that stimulates the proliferation of primitive hematopoietic and nonhema-topoietic cells [7]. In vitro, SCF has minimal effect on hematopoietic and nonhematopoietic progenitor cells, but it synergistically increases the activity of other hematopoietic growth factors, such as G-CSF, GM-CSF, and EPO. SCF stimulates the generation of dendritic cells in vitro and mast cells in vivo. 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Neutropenia is a drop in the number of circulating leukocytes, especially neutrophils. It can be induced by a variety of drugs. Treatment with cytotoxic antineo-plastic drags usually results in severe neutropenia, which can be treated with colony-stimulating factors (G-CSF, GM-CSF). 

G-protein-coupled Receptor Kinases (GRKs) G-protein-coupled Receptors G-proteins and Wnt Signaling Granulocyte-CSF (G-CSF) Granulocyte-macrophage-CSF (GM-CSF)... 

Sustained NF-kB activation, TNF-a, IL-1, proliferation, signals (M-CSF, G-CSF), chemotaxis (MCP-1), adhesion (VCAM-1, ICAM-1), thrombogenesis (TF)... 

Rheumatoid synovial cells produce a broad range of cytokines (Brennan et al., 1991). The formation of IL-la, IL-1 /3, GM-CSF, G-CSF, TNFa and other cytokines may be under the direct influence of ox-LDL and/or... 

G-CSF Granulocyte colony-stimulating factor GDP Guanosine 5 -diphosphate GEC Glomerular epithelial cell GF-1 An insulin-like growth factor GFR Glomerular filtration rate... 

There is much controversy regarding the routine use of colony-stimulating factors (e.g., G-CSF and GM-CSF) in neutropenic patients. Even though several clinical trials have shown... 

G-CSF Granulocyte colony-stimulating factor HS At bedtime horn somni)... 

Flomenberg N, Devine SM, DiPersio JF, et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 2005 106 1867-74. 

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