title: Anti-inflammatory effect of intravenous immunoglobulin in comparison with dexamethasone in vitro: implication for treatment of Kawasaki disease.
abstract: 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.
authors.affiliation: Department of Pediatrics, Yamaguchi University School of Medicine, 1-1-1 Minami-kogushi, Ube, 755-8505, Yamaguchi, Japan.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Makata
authors.forename: Takashi
authors.initials: T
authors.lastname: Ichiyama
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Uchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takekawa
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Matsubara
authors.forename: Susumu
authors.initials: S
authors.lastname: Furukawa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D003907:Dexamethasone / Q000494:pharmacology*; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy; D016328:NF-kappa B / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D019040:E-Selectin; D016756:Immunoglobulins, Intravenous; D015850:Interleukin-6; D016328:NF-kappa B; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone