Protective effect of granulocyte-colony stimulating factor against amphotericin B-induced myelosuppression in vitro.
Amphotericin B causes suppression of bone marrow (BM) progenitor cells in vitro. Granulocyte colony stimulating factor (G-CSF) enhances the proliferation of myeloid cells. The present study defines the role of G-CSF in preventing amphotericin B-induced myelosuppression. G-CSF increased the proliferative potential of BM and protected against amphotericin B-induced myelosuppression if it was added to the medium during the early phase of exposure of BM to amphotericin B. Monoclonal antibodies to tumour necrosis factor-alpha (TNF) or interferon-gamma (IFN) inhibited the myelosuppression partially; simultaneous presence of both these antibodies completely abrogated this suppression, suggesting that both TNF alpha and IFN gamma were involved in amphotericin-induced myelosuppression. TNF- or IFN-induced suppression of BM was also inhibited by G-CSF. These data suggest that G-CSF prevents the amphotericin B-induced myelosuppression by antagonizing the suppressive effects of TNF and IFN and by enhancing the proliferative activity of BM.
Charak
B S
BS
Bone Marrow Transplantation Program, Georgetown University, Washington, D.C.
Brown
E G
EG
Mazumder
A
A
D000666:Amphotericin B / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000502:physiology; D007700:Kinetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D000666:Amphotericin B; D007371:Interferon-gamma