Yamamoto Sayaka, Ishida Tatsuhiro, Inoue Akiko, Mikami Junko, Muraguchi Masahiro, Ohmoto Yasukazu, Kiwada Hiroshi
Department of Pharmacokinetics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1, Sho-machi, 770-8505, Tokushima, Japan.
Int J Pharm. 2002 Apr 2;236(1-2):125-33. doi: 10.1016/s0378-5173(02)00026-1.
The immune response caused by liposome stimulation was studied by assessing the level of several cytokines released from human peripheral blood cells. Liposome stimulation resulted in the release of IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma. The size of the liposomes affected the degree of the cytokine releases with larger sized liposomes causing higher levels of cytokine induction. In addition, it appears that the lipid composition of liposomes had no effect on the degree of cytokine release. The release of cytokines occurred even in the absence of serum, suggesting that serum proteins did not contribute to liposome stimulation in peripheral blood cells. The release of cytokines induced by liposome stimulation was inhibited by the presence of either protein kinase-C (PKC) or protein tyrosine kinase (PTK) inhibitor, but not by the presence of an endocytosis inhibitor. This indicates that signal transduction via PKC or PTK is necessary, in order for human peripheral blood cells to release cytokines (IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma) as the result of liposome stimulation. These quantitative data on the release of cytokines by liposomal stimulation provide useful information for the development of rational drug delivery systems and the safety of cytokine induction via the use of liposomes.
通过评估从人外周血细胞释放的几种细胞因子的水平，研究了脂质体刺激引起的免疫反应。脂质体刺激导致白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的释放。脂质体的大小影响细胞因子释放的程度，较大尺寸的脂质体导致更高水平的细胞因子诱导。此外，脂质体的脂质组成似乎对细胞因子释放程度没有影响。即使在没有血清的情况下也会发生细胞因子的释放，这表明血清蛋白对外周血细胞中的脂质体刺激没有作用。脂质体刺激诱导的细胞因子释放受到蛋白激酶-C（PKC）或蛋白酪氨酸激酶（PTK）抑制剂的抑制，但不受内吞作用抑制剂的抑制。这表明，为了使人外周血细胞因脂质体刺激而释放细胞因子（IL-6、IL-10、IL-1β、TNF-α和IFN-γ），通过PKC或PTK的信号转导是必要的。这些关于脂质体刺激引起的细胞因子释放的定量数据为合理药物递送系统的开发以及通过使用脂质体诱导细胞因子的安全性提供了有用的信息。
