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 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.
Terai
M
M
Department of Pediatrics, Chiba University School of Medicine, Chiba-shi, Japan. terai@med.m.chiba-u.ac.jp
Jibiki
T
T
Harada
A
A
Terashima
Y
Y
Yasukawa
K
K
Tateno
S
S
Hamada
H
H
Oana
S
S
Niimi
H
H
Matsushima
K
K
D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000097:blood* / Q000378:metabolism; D054407:Chemokine CCL4; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000097:blood / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood* / Q000378:metabolism / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D005719:gamma-Globulins / Q000627:therapeutic use*
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D007375:Interleukin-1; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha; D005719:gamma-Globulins; D002118:Calcium