Granulocyte colony-stimulating factor has no adverse effects on atherosclerotic lesions in high cholesterol-fed miniature Swine.
Granulocyte colony-stimulating factor (G-CSF) is widely used to mobilize peripheral blood stem cells, and expected to restore cardiac function for patients with coronary artery diseases as a consequence of progression of atherosclerosis. Safety issues related to the administration of G-CSF to these patients, however, are still under study. The animal model for atherosclerosis was produced by feeding miniature swine a high-cholesterol diet for 3 months. G-CSF (5 or 10 microg/kg/day) was given to the animal model by daily subcutaneous injections for 10 days and 20 main arteries were evaluated pathologically. In addition, the general toxicological effects were studied on clinical signs, body weight, hematology, blood chemistry and pathology. In the G-CSF-treated groups, a variety of changes related to the major pharmacological activity of G-CSF including an increase in white blood cell (WBC) counts were observed. In many arteries, atherosclerotic lesions similar to Type I-V of the proposed classification by the American Heart Association were observed. No effects of the G-CSF treatment were seen on the histopathological findings, incidence, severity or distribution of atherosclerotic lesions. In addition, no infiltration of neutrophils to the lesions was observed. These findings suggest that the administration of G-CSF causes neither exacerbation or modification of atherosclerotic lesions nor adverse changes despite that a sufficient increase in WBC counts could be achieved in the peripheral blood.
Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. takaihrt@chugai-pharm.co.jp
Hirotake
H
Takai
Akio
A
Miyoshi
Masaki
M
Yamazaki
Kenji
K
Adachi
Kouichi
K
Katagiri
Hitoshi
H
Arakawa
Kiyoka
K
Katsuyama
Tsuneo
T
Ito
Etsuko
E
Fujii
Shuji
S
Hayashi
Atsuhiko
A
Kato
Masami
M
Suzuki
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D001774:Blood Chemical Analysis / Q000662:veterinary; D004036:Diet, Atherogenic; D004562:Electrocardiography / Q000662:veterinary; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000662:veterinary; D007279:Injections, Subcutaneous; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy* / Q000473:pathology*; D013556:Swine, Miniature
D016179:Granulocyte Colony-Stimulating Factor