Makata Haruyuki, Ichiyama Takashi, Uchi Ryutaro, Takekawa Tsuyoshi, Matsubara Tomoyo, Furukawa Susumu
Department of Pediatrics, Yamaguchi University School of Medicine, 1-1-1 Minami-kogushi, Ube, 755-8505, Yamaguchi, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Aug;373(5):325-32. doi: 10.1007/s00210-006-0084-z. Epub 2006 Aug 1.
High-dose intravenous immunoglobulin (IVIG) is a well-established standard therapy for Kawasaki disease (KD) that reduces the risk of developing coronary artery aneurysms. On the other hand, some reports have recommended an alternative therapy with steroids for KD patients. In this study we investigated the anti-inflammatory effect of IVIG in comparison with dexamethasone at clinical doses in vitro. High-dose IVIG inhibited tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappaB (NF-kappaB) to a greater degree than dexamethasone in human monocytic U937 cells and human coronary arterial endothelial cells (HCAEC), but not in human T lymphocytic Jurkat cells. IVIG was more potent than dexamethasone in reducing the expression of CD16 (FcgammaRIII) in human monocytic THP-1 cells stimulated with lipopolysaccharide and in Jurkat cells stimulated with dimethyl sulfoxide. In HCAEC exposed to TNF-alpha, IVIG and dexamethasone inhibited interleukin-6 production to a similar degree, whereas the expression of E-selectin was inhibited more strongly by IVIG. Our results show that high-dose IVIG inhibits the activation of monocytes/macrophages and coronary arterial endothelial cells more strongly than that of T cells, whereas dexamethasone inhibits the activation of all three cell types. These findings suggest that IVIG or dexamethasone therapy should be chosen to match the types of cells that are activated during acute KD.
大剂量静脉注射免疫球蛋白（IVIG）是川崎病（KD）公认的标准治疗方法，可降低冠状动脉瘤的发生风险。另一方面，一些报告推荐对KD患者采用类固醇替代疗法。在本研究中，我们在体外比较了IVIG与临床剂量地塞米松的抗炎作用。在人单核细胞U937细胞和人冠状动脉内皮细胞（HCAEC）中，高剂量IVIG比地塞米松更能抑制肿瘤坏死因子-α（TNF-α）诱导的核因子-κB（NF-κB）激活，但在人T淋巴细胞Jurkat细胞中则不然。在脂多糖刺激的人单核细胞THP-1细胞和二甲基亚砜刺激的Jurkat细胞中，IVIG比地塞米松更有效地降低CD16（FcγRIII）的表达。在暴露于TNF-α的HCAEC中，IVIG和地塞米松对白细胞介素-6产生的抑制程度相似，而IVIG对E-选择素表达的抑制作用更强。我们的结果表明，高剂量IVIG比T细胞更强烈地抑制单核细胞/巨噬细胞和冠状动脉内皮细胞的激活，而地塞米松则抑制所有三种细胞类型的激活。这些发现表明，应根据急性KD期间激活的细胞类型选择IVIG或地塞米松治疗。
