Hematopoietic growth factors: biology and clinical application

A number of recently identified cytokines have been implicated in the development of blood cells and their functional activation. These include granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukins-1, -3, and -6. The two that have been studied most extensively clinically are G- and GM-CSF. Biologic differences between these two agents have important implications for their use in particular clinical settings. Whereas G-CSF for the most part has demonstrated lineage specificity in stimulating production of neutrophil granulocytes, GM-CSF stimulates production of all types of granulocytes and is a potent activator of monocytes and macrophages as well. In addition, GM-CSF has been found to induce other cytokines, such as tumor necrosis factor and interleukin-1. Functional differences such as influencing neutrophil migration have also been noted; GM-CSF can be a potent inhibitor of neutrophil migration. The interaction of these and other cytokines in inflammation and injury is the determinant of the ultimate clinical outcome. Potential clinical applications for these growth factors are discussed, and specific clinical studies during which recombinant human G-CSF was used are reviewed.