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.
Joseph
Jacob
J
Department of Medicine, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA. jacob.joseph@med.va.gov
Rimawi
Asem
A
Mehta
Paulette
P
Cottler-Fox
Michele
M
Sinha
Anjan
A
Singh
Balkrishnaman K
BK
Pacheco
Rebecca
R
Smith
Eugene S
ES
Mehta
Jawahar L
JL
D000368:Aged; D000369:Aged, 80 and over; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor