Role of granulocyte colony-stimulating factor in preventing ceftazidime-induced myelosuppression in vitro.
Ceftazidime has been reported to cause myelosuppression both in vitro and in vivo. Granulocyte colony-stimulating factor (G-CSF) is known to enhance the proliferation and differentiation of myeloid cells. The present study was carried out to define the role of G-CSF in preventing the ceftazidime-induced suppression of BM progenitor cells in vitro, and to define the mechanisms involved in ceftazidime-induced myelosuppression. Our results show that G-CSF was able to maintain the proliferative activity of BM cells in the presence of ceftazidime if it was added to the culture medium during the early phase of exposure of BM to ceftazidime. Monoclonal antibody to TNF completely inhibited the ceftazidime-induced myelosuppression. The suppressive effect on BM was mediated via CD3+ T cells whereas macrophages conferred protection against this suppression. TNF-induced suppression of BM was inhibited by G-CSF. These data suggest that G-CSF prevents the ceftazidime-induced myelosuppression by antagonizing the suppressive effect of TNF and by enhancing the proliferative activity of BM.
Charak
B S
BS
Bone Marrow Transplantation Program, Georgetown University, Washington DC 20007, USA.
Brown
E G
EG
Mazumder
A
A
D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D017252:CD3 Complex / Q000096:biosynthesis; D002442:Ceftazidime / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004336:Drug Antagonism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017252:CD3 Complex; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D002442:Ceftazidime