Phillips K, Arai M, Tanabe T, Raskin R, Volz M, Uhl E W, Yamamoto J K
Department of Pathobiology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA.
Vet Immunol Immunopathol. 2005 Dec 15;108(3-4):357-71. doi: 10.1016/j.vetimm.2005.06.010. Epub 2005 Aug 10.
The hematological and virological effects of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) were evaluated in feline immunodeficiency virus (FIV)-infected cats. Six age-matched, FIV-infected cats used in this cross-over study were injected subcutaneously with 5 microg/kg of rHuG-CSF daily for 3 weeks, while six control cats received a placebo. Five of six rHuG-CSF-treated cats had significant increases in neutrophil counts that peaked on days 11-21 of treatment. All rHuG-CSF-treated cats exhibited an increase in myeloid:erythroid ratios of the bone marrow cells without significant changes in lymphocyte, CD4 counts, CD4/CD8 ratios, RBC counts, FIV antibody titers, and FIV loads in peripheral blood, and without clinical and hematological toxicities. Five of six rHuG-CSF-treated cats developed antibodies to rHuG-CSF by 14-21 days of treatment, which correlated with decreasing neutrophil counts and increasing neutralizing antibodies to rHuG-CSF. Three cats re-treated with rHuG-CSF rapidly developed neutralizing antibodies to rHuG-CSF, while one cat also developed neutralizing antibodies to recombinant feline G-CSF (rFeG-CSF). Overall, rHuG-CSF treatment increased neutrophil counts in FIV-infected cats without affecting the infection status of cats. However, long-term use of rHuG-CSF is not recommended in cats because of the neutralizing antibody production to rHuG-CSF that affects the drug activity. In addition, a preliminary finding suggests that repeated treatment cycle can also induce cross-neutralizing antibodies to rFeG-CSF, which may potentially affect the homeostasis of endogenous FeG-CSF.
在感染猫免疫缺陷病毒（FIV）的猫中评估了重组人粒细胞集落刺激因子（rHuG-CSF）的血液学和病毒学效应。在这项交叉研究中，六只年龄匹配、感染FIV的猫每天皮下注射5微克/千克的rHuG-CSF，持续3周，而六只对照猫接受安慰剂。六只接受rHuG-CSF治疗的猫中有五只中性粒细胞计数显著增加，在治疗的第11至21天达到峰值。所有接受rHuG-CSF治疗的猫骨髓细胞的髓系：红系比例均增加，外周血淋巴细胞、CD4计数、CD4/CD8比例、红细胞计数、FIV抗体滴度和FIV载量无显著变化，且无临床和血液学毒性。六只接受rHuG-CSF治疗的猫中有五只在治疗14至21天时产生了针对rHuG-CSF的抗体，这与中性粒细胞计数减少和针对rHuG-CSF的中和抗体增加相关。三只再次接受rHuG-CSF治疗的猫迅速产生了针对rHuG-CSF的中和抗体，而一只猫还产生了针对重组猫G-CSF（rFeG-CSF）的中和抗体。总体而言，rHuG-CSF治疗增加了感染FIV的猫的中性粒细胞计数，而不影响猫的感染状态。然而，由于产生影响药物活性的针对rHuG-CSF的中和抗体，不建议在猫中长期使用rHuG-CSF。此外，一项初步发现表明，重复治疗周期也可诱导针对rFeG-CSF的交叉中和抗体，这可能会潜在影响内源性FeG-CSF的稳态。
