Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates

J Exp Med. 1987 Apr 1;165(4):941-8. doi: 10.1084/jem.165.4.941.

Abstract

We examined the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in the peripheral white blood cells (WBC) was seen, reaching a plateau after 1 wk of rhG-CSF treatment. The elevation of WBC was due to an increase in the absolute neutrophil count. These results demonstrate that rhG-CSF is a potent granulopoietic growth and differentiation factor in vivo. In cyclophosphamide (CY)-induced myelosuppression, rhG-CSF was able to shorten the time period of WBC recovery in two treated monkeys to 1 wk, as compared to more than 4 wk for the control monkey. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Colony-Stimulating Factors / pharmacology*
  • Cyclophosphamide / toxicity
  • Granulocytes
  • Hematopoiesis / drug effects*
  • Humans
  • Macaca fascicularis
  • Macrophages
  • Neutrophils / physiology
  • Pancytopenia / chemically induced
  • Pancytopenia / pathology
  • Recombinant Proteins / pharmacology
  • Spleen / drug effects

Substances

  • Colony-Stimulating Factors
  • Recombinant Proteins
  • Cyclophosphamide