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Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma
1Department of Pediatrics, Chiba University School of Medicine, Chiba-shi, Japan. terai@med.m.chiba-u.ac.jp
Insights
Monocyte chemoattractant protein-1 (MCP-1) is involved in Kawasaki disease (KD) vasculitis. Gamma globulin (GG) treatment reduces MCP-1 levels and activity, suggesting a therapeutic mechanism for KD.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Pediatric Rheumatology
Background:
- Kawasaki disease (KD) is a critical pediatric vasculitis affecting coronary arteries.
- Monocyte and macrophage infiltration is a hallmark of KD vascular lesions.
- Monocyte chemoattractant protein-1 (MCP-1) is a key chemokine for monocyte recruitment.
Purpose of the Study:
- To investigate the role of MCP-1 in Kawasaki disease pathogenesis.
- To determine the effect of gamma globulin (GG) treatment on MCP-1 levels and activity in KD.
Main Methods:
- Immunohistochemistry on cardiac tissues from fatal KD cases.
- Measurement of circulating cytokine levels (MCP-1, IL-8, TNF-alpha, IL-1alpha) before and after GG treatment.
- Western blotting to assess MCP-1 binding to GG.
- In vitro assays evaluating GG's effect on MCP-1-induced calcium influx in monocytic cells.
Main Results:
- MCP-1 was localized in vascular lesions of KD patients, correlating with inflammation.
- Elevated circulating MCP-1 levels were observed in KD patients before GG treatment.
- GG treatment significantly decreased MCP-1 levels and inhibited MCP-1 activity in vitro.
- MCP-1 was found to bind to GG.
Conclusions:
- MCP-1 plays a significant role in the inflammatory process of Kawasaki disease vasculitis.
- Gamma globulin therapy may exert its beneficial effects by neutralizing MCP-1 activity.
- Targeting MCP-1 could be a potential therapeutic strategy for KD.
Abstract:
Kawasaki disease (KD) is a systemic vasculitis preferentially affecting coronary arteries. Extensive monocytes/macrophages infiltrate in the vascular lesions, implying the involvement of a chemotactic cytokine in their recruitment. We investigated the role of monocyte chemoattractant protein-1 (MCP-1, also termed monocyte chemotactic and activating factor) in KD. In the immunohistochemical studies using the cardiac tissues of patients with fatal KD, MCP-1 but not interleukin (IL) -8 or macrophage inflammatory protein-1alpha was localized at the extracellular matrix associated with mononuclear cellular infiltration. The sites of MCP-1 expression correlated with the distribution of the acute inflammation, including early coronary vasculitis. In prospectively studied patients with KD, circulating levels of MCP-1, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-1alpha 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 control values. GG treatment correlated with a rapid decrease in the circulating 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-1-induced Ca2+ influx in a human monocytic cell line in vitro. These findings suggest a role of MCP-1 in KD, and indicate that GG treatment may block MCP-1 activity, thus alleviating KD vasculitis.