The hematopoietic growth factors are a family of glycoproteins that stimulate the production and activation of blood cells. These factors, called colony stimulating factors (CSF) or interleukins (IL), have been defined largely via in vitro studies, cloned using recombinant DNA technology, and are now in the early stages of clinical trials. However the precise role(s) they play in vivo are not clear, and their functional interrelationships remain unknown. Recent studies have shown that when dogs are treated with recombinant human granulocyte colony stimulating factor (rhG-CSF), they have a brief neutrophilia followed by a prolonged period of severe neutropenia. Sera from dogs with neutropenia contain antibody to rhG-CSF, block in vitro colony growth as well as neutrophilia in vivo stimulated by rhG-CSF, and appear to clock endogenous canine G-CSF action. Using this model system, the studies propose to explore the in vivo relationship of G-CSF and granulocyte macrophage CSF (GMCSF). Studies to be performed include a direct comparison of rhGMCSF to rhG-CSF immunization, measurement of the response to rhGM-CSF and rhG-CSF immunized dogs, and neutrophil kinetics studies to define the pathophysiologic mechanism of the neutropenia. Further studies will examine the role of G-CSF in neutrophilia stimulated by physiologic stimuli such as endotoxin, and the compensatory responses of dogs made neutropenia by immunization with rhG-CSF. Finally studies will be performed with recombinant canine G-CSF in normal and neutropenia dogs to assess the specificity of the immunization. Through such studies further definition of the in vivo interrelationships of the hematopoietic growth factors should be possible, making more rational future attempts to stimulate blood cell production.
| Kothari, S S; Abrahamsen, M S; Cole, T et al. (1995) Expression of granulocyte colony stimulating factor (G-CSF) and granulocyte/macrophage colony stimulating factor (GM-CSF) mRNA upon stimulation with phorbol ester. Blood Cells Mol Dis 21:192-200 |
