新喋呤
外周血单个核细胞
肿瘤坏死因子α
重组DNA
单核细胞
免疫学
相伴的
白细胞介素
生物
药理学
医学
细胞因子
内科学
体外
基因
生物化学
作者
Danuta J. Herzyk,Jeanne M. Soos,Curtis C. Maier,Elizabeth R. Gore,Padma K. Narayanan,Kimberly Nadwodny,Susan Liu,Zdenka L. Jonak,Peter J. Bugelski
出处
期刊:Cytokine
[Elsevier]
日期:2002-10-01
卷期号:20 (1): 38-48
被引量:14
标识
DOI:10.1006/cyto.2002.1978
摘要
Recombinant human interleukin (IL)-18 (rHuIL-18) has a potential as a therapeutic agent in cancer and is currently in drug development. Since human IL-18 displays 96% and 100% amino acid sequence homology with cynomolgus monkey and chimpanzee IL-18, respectively, the biological responses to rHuIL-18 were evaluated in these species. A single intravenous dose of rHuIL-18 at 1 or 10mg/kg in cymonolgus monkeys caused a transient reduction in lymphocyte counts, induction of IL-1alpha and tumour necrosis factor alpha (TNF-alpha) mRNA in whole blood cells and a marked increase in plasma neopterin. rHuIL-18 administered to cynomolgus monkeys at doses of 0.3 or 3mg/kg for two 5-day cycles (Days 1-5 and 15-19) resulted in increased monocyte counts, induction of NK cells and concomitant increases in plasma IL-12 and neopterin. Administration of repeat doses of rHuIL-18 at 10mg/kg to chimpanzees was associated with increased monocyte counts, upregulation of FcgammaRI surface expression on monocytes, and increased IL-8, IL-12 and neopterin in plasma. These studies demonstrate, for the first time, the immunostimulatory activity of rHuIL-18 in vivo. The described pharmacological profile of rHuIL-18 in both cynomolgus monkeys and chimpanzees is indicative of the immunotherapeutic potential of rHuIL-18 in the treatment of cancer.
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