Department of Anesthesiology, Kansai Medical University, Osaka, Japan.
J Immunotoxicol. 2011 Oct-Dec;8(4):359-66. doi: 10.3109/1547691X.2011.620036. Epub 2011 Oct 28.
Propofol is an intravenous anesthetic that is widely used for anesthesia and sedation. Dendritic cells (DC) are one of the crucial immune cells that bridge innate and adaptive immunity, in which DC process antigens during innate immune responses to present them to naïve T-cells, leading to an establishment of adaptive immunity. Prostaglandin (PG)-E(2) may be secreted by DC into the microenvironment, considerably influencing DC phenotype and function, and thus determining the fate of adaptive immunity. Since propofol suppresses PGE(2) production in murine macrophages, the primary purpose of the present study was to determine whether propofol also suppresses PGE(2) production in DC. Assuming a positive finding of such suppression, we tested whether this also leads to alterations of interleukin (IL)-12 and IL-10 production and DC surface marker expression, both of which can be modulated by PGE(2). In bone marrow-derived DC, propofol significantly suppressed the PGE(2) production after lipopolysaccharide stimulation. Cyclo-oxygenase (COX) protein expression and arachidonic acid release were unaffected, while COX enzyme activity was significantly inhibited by propofol. The propofol-induced COX inhibition did not lead to the increased production of cysteinyl leukotrienes and leukotriene-B(4). Endogenous COX inhibition with propofol, as well as with the selective COX-2 inhibitor, NS-398, did not affect IL-12 and IL-10 production from DC. The surface expression of I-A(b) and CD40 on DC was not changed, while that of CD86 slightly increased, with both propofol and NS-398; expression of CD80 was not affected with propofol, but increased slightly with NS-398. Finally, endogenous COX inhibition with either propofol or NS-398 did not significantly affect the ability of DC to induce allogeneic T-cell proliferation. It is concluded that the intravenous anesthetic propofol suppresses COX enzyme activity in DC, with no consequences with respect to IL-12/IL-10 production and allogeneic T-cell proliferation, while minimal consequences were observed in surface molecule expression.
异丙酚是一种广泛用于麻醉和镇静的静脉麻醉剂。树突状细胞（DC）是连接先天免疫和适应性免疫的关键免疫细胞之一，在先天免疫反应中，DC 处理抗原并将其呈递给幼稚 T 细胞，从而建立适应性免疫。前列腺素（PG）-E（2）可能由 DC 分泌到微环境中，极大地影响 DC 的表型和功能，从而决定适应性免疫的命运。由于异丙酚抑制鼠巨噬细胞中 PGE（2）的产生，本研究的主要目的是确定异丙酚是否也抑制 DC 中 PGE（2）的产生。假设这种抑制作用为阳性，我们测试了这是否也会导致白细胞介素（IL）-12 和 IL-10 产生以及 DC 表面标志物表达的改变，这些都可以被 PGE（2）调节。在骨髓来源的 DC 中，脂多糖刺激后异丙酚显著抑制 PGE（2）的产生。环加氧酶（COX）蛋白表达和花生四烯酸释放不受影响，而 COX 酶活性被异丙酚显著抑制。异丙酚诱导的 COX 抑制不会导致半胱氨酰白三烯和白三烯 B（4）的产生增加。用异丙酚和选择性 COX-2 抑制剂 NS-398 进行内源性 COX 抑制均不影响 DC 产生 IL-12 和 IL-10。DC 表面 I-A（b）和 CD40 的表达没有改变，而 CD86 的表达略有增加，异丙酚和 NS-398 均如此；CD80 的表达不受异丙酚影响，但 NS-398 略有增加。最后，用异丙酚或 NS-398 进行内源性 COX 抑制均不显著影响 DC 诱导同种异体 T 细胞增殖的能力。结论：静脉麻醉剂异丙酚抑制 DC 中的 COX 酶活性，但对 IL-12/IL-10 产生和同种异体 T 细胞增殖没有影响，而表面分子表达仅有轻微影响。
