ABSTRACT
SD/01, a sustained-duration molecule, has been developed by adding a poly [ethylene glycol] molecule to the filgrastim molecule. The pegylation does not change the properties of filgrastim, except that the plasma clearance is decreased and plasma half-life is increased. Increasing the duration of the biological effects of filgrastim may offer certain groups of patients better benefits. Early clinical studies have been encouraging with no serious toxicities noted.
Subject(s)
Granulocyte Colony-Stimulating Factor/pharmacokinetics , Animals , Filgrastim , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Mobilization/methods , Humans , Neutropenia/drug therapy , Recombinant ProteinsABSTRACT
Twenty-four healthy male volunteers received either placebo or 75, 150, or 300 microg filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) for 12 days to study effects on monocytes and lymphocytes. In all filgrastim-treated groups, tumor necrosis factor alpha (TNF-alpha), interleukin-12 (IL-12), and interferon gamma (IFN-gamma) release by whole blood in response to endotoxin (lipopolysaccharide) was reduced. IL-12 added in vitro to lipopolysaccharide-stimulated blood of filgrastim-treated donors restored IFN-gamma and TNF-alpha release, suggesting that the anti-inflammatory effect of granulocyte colony-stimulating factor is exercised through IL-12 suppression. Phytohemagglutinin- or anti-CD3 antibody-induced lymphocyte proliferation ex vivo was reduced by 60% from day 5 to day 15, after a 50% increase at day 2 with concomitant doubled IL-2 release. In vivo, filgrastim induced doubling of all T-cell populations by day 8. Filgrastim decreased proinflammatory cytokine production and lymphocyte proliferation ex vivo throughout prolonged treatment at all doses. This indicates that endogenous granulocyte colony-stimulating factor may counterregulate the inflammatory cytokine cascade and implies a potential indication for filgrastim in chronic inflammatory conditions.
Subject(s)
Cytokines/drug effects , Granulocyte Colony-Stimulating Factor/pharmacology , Lymphocytes/drug effects , Adult , Cell Division/drug effects , Double-Blind Method , Filgrastim , Humans , Interferon-gamma/drug effects , Interleukin-12/blood , Killer Cells, Natural/drug effects , Leukocyte Count/drug effects , Lipopolysaccharides , Male , Monocytes/drug effects , Recombinant Proteins , Reference Values , Time Factors , Tumor Necrosis Factor-alpha/drug effectsABSTRACT
Stem cell factor (SCF) is a hematopoietic growth factor which acts on both primitive and mature progenitors cells. In animals, high doses of SCF alone stimulate increases in cells of multiple lineages and mobilize peripheral blood progenitor cells (PBPC). Phase I studies of rhSCF have demonstrated dose related side effects which are consistent with mast cell activation. Based upon in vitro synergy between SCF and G-CSF we have demonstrated the potential of low doses of SCF to synergize with G-CSF to give enhanced mobilization of PBPC. These PBPC have increased potential for both short and long term engraftment in lethally irradiated mice and lead to more rapid recovery of platelets. On going Phase I/II studies with rhSCF plus rhG-CSF for mobilization of PBPC, demonstrated similar increases in PBPC compared to rhG-CSF alone. These data suggest a clinical role of rhSCF in combination with rhG-CSF for optimal mobilization of PBPC.
Subject(s)
Hematopoietic Cell Growth Factors/pharmacology , Hematopoietic Stem Cells/drug effects , Animals , Colony-Stimulating Factors/administration & dosage , Leukapheresis , Mice , Papio , Recombinant Proteins/pharmacology , Stem Cell FactorABSTRACT
Thorough and accurate fulfillment of the GIA's role is integral to the successful completion of endoscopic procedures. Strong basic nursing skills, a well-developed knowledge of gastrointestinal anatomy and physiology, and a thorough understanding of endoscopic equipment and accessories are required for the fulfillment of the GIA's role. Clear communication and cooperation between the nurses, associates, and physicians creates a team approach that optimizes patient care.
