Arai M, Darman J, Lewis A, Yamamoto J K
Department of Pathobiology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611, USA.
Vet Immunol Immunopathol. 2000 Nov 23;77(1-2):71-92. doi: 10.1016/s0165-2427(00)00232-4.
Recombinant human GM-CSF (rhGM-CSF) and erythropoietin (rhEPO) were tested on chronically FIV-infected laboratory cats and uninfected specific-pathogen-free (SPF) cats. In Study 1, a total of eight cats (four cats per group of either infected or uninfected cats) received subcutaneous injection (twice a day) for 2 weeks with 5 microg/kg of rhGM-CSF, while seven cats (three SPF and four FIV-infected cats) served as the placebo-treated control cats. Four of eight rhGM-CSF-treated cats (two cats each from infected and uninfected groups) developed elevated WBC counts which peaked at Days 5-8 of treatment when compared to placebo-treated cats. The elevated WBC counts were attributed to the increase in either neutrophils, lymphocytes, eosinophils, monocytes, or their combinations. The RBC counts, platelet counts, and blood chemistry were not significantly affected by the treatment. Anti-rhGM-CSF antibodies were detected in six of eight rhGM-CSF-treated cats by Day 35 post-first treatment. All rhGM-CSF-treated infected cats but no placebo-treated infected cats had 1-2 log increase in FIV load in the PBMC during the treatment. In vitro studies suggest that rhGM-CSF has an effect on FIV replication in T cells but not in alveolar macrophages. Five of eight rhGM-CSF-treated cats had low-grade fever at 3-6 days of treatment. In Study 2, four cats per group of either infected or uninfected cats were treated (subcutaneously once a day) three times a week for 2 weeks with 100U/kg of rhEPO and monitored as before, while seven cats (three SPF and four FIV-infected cats) served as the placebo-treated control cats. All rhEPO-treated cats had a gradual increase in RBC, Hgb, and PCV counts which peaked at 2-4 weeks post-first rhEPO treatment, whereas none of the placebo-treated cats had significant increase in these parameters. The rhEPO-treated cats also developed elevated WBC counts consisting of either elevated neutrophils, lymphocytes, or their combination by 4 weeks post-first treatment but there was no statistical difference between rhEPO-treated and placebo-treated groups. None of the cats developed anti-rhEPO antibodies and no remarkable changes in blood chemistry, clinical signs, and FIV loads or FIV antibody titers were observed. Overall, rhEPO can be used safely on FIV-infected cats but the use of rhGM-CSF on FIV-infected cats should be performed with discretion.
重组人粒细胞-巨噬细胞集落刺激因子（rhGM-CSF）和促红细胞生成素（rhEPO）在慢性感染猫免疫缺陷病毒（FIV）的实验猫和无特定病原体（SPF）的未感染猫身上进行了测试。在研究1中，总共8只猫（感染或未感染猫每组4只）接受皮下注射（每天两次），持续2周，剂量为5微克/千克的rhGM-CSF，而7只猫（3只SPF猫和4只FIV感染猫）作为安慰剂治疗的对照猫。与接受安慰剂治疗的猫相比，8只接受rhGM-CSF治疗的猫中有4只（感染组和未感染组各2只）白细胞计数升高，在治疗的第5 - 8天达到峰值。白细胞计数升高归因于中性粒细胞、淋巴细胞、嗜酸性粒细胞、单核细胞或它们的组合增加。治疗对红细胞计数、血小板计数和血液化学指标没有显著影响。在首次治疗后第35天，8只接受rhGM-CSF治疗的猫中有6只检测到抗rhGM-CSF抗体。在治疗期间，所有接受rhGM-CSF治疗的感染猫外周血单核细胞（PBMC）中的FIV载量增加了1 - 2个对数，而接受安慰剂治疗的感染猫则没有。体外研究表明，rhGM-CSF对T细胞中的FIV复制有影响，但对肺泡巨噬细胞没有影响。8只接受rhGM-CSF治疗的猫中有5只在治疗的第3 - 6天出现低热。在研究2中，感染或未感染猫每组4只猫接受皮下注射（每天一次），每周3次，持续2周，剂量为100单位/千克的rhEPO，并如前一样进行监测，而7只猫（3只SPF猫和4只FIV感染猫）作为安慰剂治疗的对照猫。所有接受rhEPO治疗的猫红细胞、血红蛋白和血细胞比容计数逐渐增加，在首次rhEPO治疗后2 - 4周达到峰值，而接受安慰剂治疗的猫这些参数均无显著增加。接受rhEPO治疗的猫在首次治疗后4周时白细胞计数也升高，由中性粒细胞、淋巴细胞升高或它们的组合导致，但rhEPO治疗组和安慰剂治疗组之间没有统计学差异。没有猫产生抗rhEPO抗体，并且在血液化学指标、临床症状、FIV载量或FIV抗体滴度方面未观察到明显变化。总体而言，rhEPO可安全用于FIV感染的猫，但rhGM-CSF在FIV感染猫身上的使用应谨慎。
