Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma globulin treatment

Kawasaki disease (KD) is a systemic vasculitis preferentially affecting cor onary arteries. Extensive monocytes/macrophages infiltrate in the vascular lesions, implying the involvement of a chemotactic cytokine in their recrui tment, We investigated the role of monocyte chemoattractant protein-1 (MCP- 1, also termed monocyte chemotactic and activating. factor) in KD, In the i mmunohistochemical studies using the cardiac tissues of patients with fatal KD, MCP-1 but not interleukin (IL) -8 or macrophage inflammatory protein-1 alpha was localized at the extracellular matrix associated with mononuclea r cellular infiltration. The sites of MCP-I expression correlated with the distribution of the acute inflammation, including early corollary vasculiti s, In prospectively studied patients with KD, circulating levels of MCP-1, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-1 alpha were elevated in 73, 77, 57, and 0% of samples before gamma globulin (GG) treatment (400 mg/kg x 5 days = total 2 g/kg), respectively, compared with respective con trol values. GG treatment correlated with a rapid decrease in the circulati ng levels of MCP-1 (P = 0.001) but not IL-8 (P = 0.19) or TNF-alpha (P = 0. 33), In the sensitive Western blotting, MCP-1 bound to GG. Furthermore, GG inhibited the MCP-induced Ca2+ influx in a human monocytic cell line in vit ro. These findings suggest a role of MCP-1 in KD, and indicate that GG trea tment may block MCP-1 activity, thus alleviating KD vasculitis.