Yoshino T, Sato K
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
Jpn J Antibiot. 1992 Jan;45(1):106-11.
A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW-2228, has some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. Recently, the application of G-CSF against infectious diseases has been considered, and some animal experiments have been carried out to support its clinical applications. In this paper, we investigated protective effects of KW-2228 against systemic infections caused by Klebsiella pneumoniae in mice with leukopenia induced by the administration of cyclophosphamide. KW-2228 (1 microgram/mouse) was administered (s.c.) once a day for 4 days following cyclophosphamide administration, then mice were challenged with K. pneumoniae (i.p.) 4 hours after the last administration of KW-2228. An antibiotic was administered (s.c., p.o.) 2 hours after the bacterial challenge. Combination effects of KW-2228 with cefazoline, cefmetazole, ceftazidime or cefaclor were evaluated in the systemic infection with K. pneumoniae. Each combination therapy using KW-2228 with each of the cephems exhibited an excellent protective effect in comparison to the therapy with a cephem alone. These results show the possibility that KW-2228 could be of use in treating obstinate infections not successfully treated with an antimicrobial agent alone.
一种经过改良的重组人粒细胞集落刺激因子（rhG-CSF），KW-2228，具有一些优异的特性，如在体外刺激粒细胞集落形成方面具有高比活性、在血浆中具有很高的生物稳定性、良好的药代动力学特征以及在正常小鼠体内对粒细胞生成具有高效能。最近，人们考虑将G-CSF应用于治疗感染性疾病，并已开展了一些动物实验来支持其临床应用。在本文中，我们研究了KW-2228对环磷酰胺诱导的白细胞减少小鼠中由肺炎克雷伯菌引起的全身感染的保护作用。在给予环磷酰胺后，每天一次皮下注射KW-2228（1微克/小鼠），共4天，然后在最后一次注射KW-2228后4小时经腹腔注射肺炎克雷伯菌对小鼠进行攻毒。在细菌攻毒后2小时给予抗生素（皮下注射、口服）。评估了KW-2228与头孢唑林、头孢美唑、头孢他啶或头孢克洛联合应用对肺炎克雷伯菌全身感染的效果。与单独使用头孢菌素治疗相比，KW-2228与每种头孢菌素联合治疗均表现出优异的保护作用。这些结果表明KW-2228有可能用于治疗仅用抗菌药物无法成功治疗的顽固性感染。
