A specific stimulator of granulocyte colony-stimulating factor accelerates recovery from cyclophosphamide-induced neutropenia in the mouse.
We have identified a small molecular weight compound, SCH 14988, which specifically stimulates in vitro granulocyte-colony stimulating factor (G-CSF) production from activated human peripheral blood mononuclear cells and monocytes but not other cytokines or CSFs with hematoregulatory activity. In vivo administration of SCH 14988 to mice rendered neutropenic by cyclophosphamide treatment resulted in the accelerated recovery of the peripheral neutrophil compartment. This activity correlated with increased in vivo G-CSF levels and stimulation of marrow granulopoiesis, and was comparable to that of exogenously administered recombinant human G-CSF. No alterations to other leukocyte populations in peripheral blood, spleen, or the peritoneal cavity were observed. These findings suggest that SCH 14988 may be clinically useful to enhance neutrophil granulopoiesis, as well as to study the mechanisms involved in G-CSF gene regulation.
Fine
J S
JS
Schering-Plough Research Institute, Department of Immunology, Kenilworth, NJ 07033, USA.
Cai
X Y
XY
Justice
L
L
Gommoll
C P
CP
Hamilton
L D
LD
Waters
T A
TA
Narula
S K
SK
Bober
L A
LA
Grace
M J
MJ
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis*; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009287:Naphthyridines / Q000494:pharmacology* / Q000627:therapeutic use; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D016207:Cytokines; D009287:Naphthyridines; D012333:RNA, Messenger; D011994:Recombinant Proteins; C107087:SCH 14988; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide