Intravenous immunoglobulin inhibits NF-kappaB activation and affects Fcgamma receptor expression in monocytes/macrophages.

Abstract

High-dose intravenous immunoglobulin (IVIG) therapy is well established as a standard therapy for Kawasaki disease (KD) that reduces the risk of developing coronary artery aneurysms. Activation of monocytes/macrophages and tumor necrosis factor-alpha (TNF-alpha) activity are responsible for severe vascular injury in acute KD. We examined whether or not IVIG inhibits TNF-alpha-induced activation of transcription factor NF-kappaB, a factor that is essential for the expression of proinflammatory cytokines, in human monocytic U-937 cells. The inhibitory effect of IVIG on NF-kappaB activation induced by TNF-alpha was evaluated by Western blotting and flow cytometry. In addition, we examined the effect of IVIG on the expression of FcgammaIII (CD16) and FcgammaRIIb (CD32b) in U-937 cells and peripheral blood CD14+ monocytes/macrophages by flow cytometry. Western blotting demonstrated that IVIG inhibits NF-kappaB activation in U-937 cells, and flow cytometry that IVIG inhibits NF-kappaB activation in U-937 cells in a dose-related manner. Western blotting of cytoplasmic extracts of U-937 cells revealed that IVIG inhibited degradation of the IkappaBalpha protein. Moreover, flow cytometry demonstrated that IVIG decreased the expression of FcgammaRIII in U-937 cells and peripheral blood CD14+ monocytes/macrophages. However, Western blotting revealed that IVIG did not affect the quantity of FcgammaRIII protein, and PCR that IVIG did not affect the quantity of FcgammaRIII mRNA in the cells. These findings suggest that IVIG inhibits TNF-alpha-induced NF-kappaB activation in monocytes/macrophages, and blocks FcgammaRIII on the membranes of monocytes/macrophages.