Actions and therapeutic potential of G-CSF and GM-CSF in cardiovascular disease.

Despite their names, the cytokines granulocyte- and granulocyte-macrophage-colony stimulating factor (G-CSF and GM-CSF respectively) have actions far beyond simply stimulating the proliferation of neutrophil and monocyte lineage cells. A comprehensive body of evidence now exists demonstrating that G-CSF and GM-CSF effectively mobilize bone-marrow-derived progenitor cells into the peripheral circulation. These mobilized progenitor cells can be conveniently harvested for use in reconstituting bone marrow by transplantation after myelo-ablative treatment of hematological malignancies. In addition, much evidence has recently emerged to suggest that these cytokines may have multiple direct and indirect beneficial cardiovascular effects--including neovascularization of ischemic myocardium and reducing the extent of myocardial damage after infarction. Based on this knowledge and a strong safety record in hematological applications, a number of early clinical trials have evaluated the use of G-CSF or GM-CSF in patients with both acute and chronic myocardial ischemia. Although the interpretation of these trials is complicated by heterogeneity in study design, small patient numbers and methodological concerns related to appropriate selection and blinding of patients, the results of ongoing larger phase II/III trials should soon be available to determine if these agents will be useful additions to the cardiovascular armamentarium.