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 facto r (G-CSF) production from activated human peripheral blood mononuclear cells and monocytes but not other cytokines or CSFs with hemato-regul atory activity. In vivo administration of SCH 14988 to mice rendered n eutropenic by cyclophosphamide treatment resulted in the accelerated r ecovery of the peripheral neutrophil compartment. This activity correl ated with increased in vivo G-CSF levels and stimulation of marrow gra nulopoiesis, and was comparable to that of exogenously administered re combinant human G-CSF. No alterations to other leukocyte populations i n peripheral blood, spleen, or the peritoneal cavity were observed. Th ese findings suggest that SCH 14988 may be clinically useful to enhanc e neutrophil granulopoiesis, as well as to study the mechanisms involv ed in G-CSF gene regulation. (C) 1997 by The American Society of Hemat ology.