Abstract 66: High-dose IgG Completely Inhibited TNF-α-induced, But Not IL-1β-induced, G-CSF Expression By Human Coronary Artery Endothelial Cells

Abstract

High-dose intravenous IgG (IVIG) is a well-established standard therapy for Kawasaki Diseases (KD) that effectively reduces both systemic inflammation and the risk of developing coronary artery aneurysms, in approximately 80% of KD. However, some patients do not respond to IVIG and the cause of their unresponsiveness remains unclear. We previously reported that high-dose IgG specifically and completely inhibited accelerated expression of KD-related cytokines, including G-CSF, by human coronary artery endothelial cells (HCAEC) in response to TNF-α. The suppression of these cytokine genes correlated closely with functional inhibition of a transcription factor, C/EBPδ. Here we show that IL-1β-induced expression of the KD-related cytokines by HCAEC was never inhibited by high-dose IgG treatment. Furthermore, although TNF-α-induced C/EBPδ activities, as measured by gel shift assay, were completely inhibited after high-dose IgG treatment, those induced by IL-1β were not inhibited at all. Our findings suggest that C/EBPδ may play a pivotal role in the clinical effectiveness of IVIG in patients with KD. Greater understanding of the precise underlying mechanisms of IVIG on coronary artery endothelial cells may contribute to the development of novel therapeutic strategies for current IVIG-resistant patients with KD.