Safety and effectiveness of granulocyte-colony stimulating factor in mobilizing stem cells and improving cytokine profile in advanced chronic heart failure.

The objective of this study was to determine a safe and effective dose of granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells in patients with advanced heart failure and to determine its effects on the cytokine profile. Patients with advanced heart failure (n = 6) and implantable defibrillators in situ were administered G-CSF after baseline echocardiographic and laboratory evaluation, using an escalating dose schedule designed to ensure safety. The peripheral CD34+ hematopoietic stem cell count increased from 3.6 +/- 0.5/microl to 38.7 +/- 13/microl (p= 0.022) after 5 days of 5 microg/kg/day G-CSF therapy. The baseline or peak white blood cell count did not predict the stem cell response. G-CSF increased plasma levels of interleukin-10. Left ventricular ejection fraction increased significantly in the 4 patients with ischemic cardiomyopathy 9 months after treatment. No major adverse effects attributable to the drug occurred during administration or 9 months of follow-up. Our results have shown that low-dose G-CSF significantly mobilized hematopoietic stem cells in advanced heart failure and improved left ventricular function in the ischemic subset of patients. G-CSF significantly increased plasma levels of the anti-inflammatory cytokine interleukin-10, without changing pro-inflammatory cytokine levels. In conclusion, these results indicate a novel mechanism of action for the potential therapeutic benefit of G-CSF in advanced ischemic cardiomyopathy.