van Royen N et al. (2005) A pilot study on stimulation of arteriogenesis using subcutaneous application of granulocyte-macrophage colony-stimulating factor as a new treatment for peripheral vascular disease. Circulation 112: 1040–1046

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is reported to stimulate arteriogenesis leading to improved collateral blood flow in patients with coronary artery disease. van Royen et al. have recently explored the use of this growth factor for treating patients with peripheral arterial disease.

Forty patients with moderate or severe intermittent claudication (vaso-occlusive disease of the legs) were randomly assigned to receive either placebo or subcutaneous treatment with GM-CSF for 14 days. Walking distances and ankle-brachial index were assessed on day 0, 14 and 90. GM-CSF treatment was discontinued in three patients because of severe side effects (chest pain, muscle pain, hypotension and shortness of breath). Many other patients experienced less severe side effects such as skin rash and fever.

After 14 days, patients in both treatment arms could walk about 60 m further. The authors conclude that this was due to a large placebo effect, particularly as ankle-brachial index values did not increase significantly during the trial. White blood cell counts and levels of C-reactive protein increased significantly following GM-CSF therapy, and a temporary increase in the number of monocytes and CD34+ stem cells was observed. Laser Doppler flowmetry measurements indicated that GM-CSF might be beneficial for the microcirculation, but the clinical relevance of this finding is unclear.

Noting that this study was limited by patient selection and, possibly, a suboptimal dosing scheme, the authors conclude that their data do not support the use of GM-CSF for treatment of patients with this condition.