1991 Fiscal Year Final Research Report Summary
動物をモデルとした川崎病病因の免疫学的・病理学的解析
| Project/Area Number |
01570548
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Teikyo University |
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Principal Investigator |
YOSHINO Kazuya Teikyo University, Faculty of Economics, Professor, 経済学部, 教授 (70091064)
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| Co-Investigator(Kenkyū-buntansha) |
KAWA Yohko Teikyo University School of Medicine, Department of Dermatology, Assistant profe, 医学部, 助手 (10082273)
SUZUKI Keiji Gunma University, College of Medical Care and Technology, Department of Patholo, 医療技術短期大学, 教授 (40008313)
OKITSU Shoko (NEGISHI Sh) Teikyo University School of Medicine, Department of Pediatrics, Assistant profes, 医学部, 助手 (10082215)
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| Project Period (FY) |
1989 – 1991
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| Keywords | Kawasaki Disease / Interleukin 1 / Tumor necrosis factor alpha / Interleukin 6 / Lactobacillus casei / C3H / HeJ mice / animal model / cardiac involvement |
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| Research Abstract |
The ability of cell wall extract separated from Lactobacillus casei(LCWE)to stimulate peritoneal macrophages(PMC)of BALB/C and C3H/Hej mice, which produced the inflammatory cytokines such as IL-1, TNFalpha and IL-6 was evaluated. The measurement of cytokines in the MPC-cultured supernatants was assayed by the proliferative activity of thymocytes from C3H/Hej mice for IL-1 and of hybridoma B3BI cells for IL-6. TNFalpha was measured by the cytotoxic activity to L929 cells and by the enzyme-linked immunosorbent assay using polyclonal and monoclonal anti-murine TNFalpha antibodies.
In comparison with LPS, LCWE induced the production of IL-1 and TNFalpha in higher titers, and similar level of IL-6 production in BALB/C mice. In C3H/flej mice LCWE induced the three kinds of cytokine production in low level or not at all. The study of IL-1beta and TNFalpha MRNA expression of MPCs stimulated with LCWE supported the results of the level and time-kinetics of produced cytokines.
The induction of mur
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ine heart damages was performed by an injection of LCWE into the peritoneal cavity using a modified method reported by Lehman et al(1988). Surprisingly, only 48 hours after the treatment of LCWE(0.02 mg/g of body weight cardiac involvement, such as angitis (endocarditis, coronary arteritis and pericarditis were found. in both BALB/c and C3H/Hej mice. The overall frequency of cardiac damages was 69 %(9/13)and 57 %(5/14)in BALB/C and C3H/Hej mice respectively 48 hours later, whereas it was 28 %(7/25)and 8%(2/25)respectively at the fourth week. The histopathological pictures by HEstaining revealed marked cell infiltration in cardiac tissure, especially by macrophges and neutrophils. Moreover, . it was demonstrated that large and small cardiac arteries with inflammation were strongly stained by antibodies to cytokines such as IL-1, TNFalpha and IL-6 in the, ABC method.
The above results suggested that LCWE was a powerful in vivo and in vitro activators of macrophages and other cells which produced inflammatory cytokines, which caused murine cardiac involvement. It is thought that LCWE injecxted BALB/C mice would be good animal models for studying the hathogenesis of Kawasaki disease in man. Less
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[Publications] Abe, Y., Nakano, Y., Nakahara, T., Kamezawa, Y., Kato, I., Ushijima, H., Yoshino, K., Ito, S., Noma, S., Okitsu, S., Tajima, M.: "Detection of serum antibody by the antimitogen assay Against streptococcal erythrogenic toxins. Agedistibution in children and the relation to Kawasaki disease." Pediatric RES.27. 11-15 (1990)
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「研究成果報告書概要(欧文)」より
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[Publications] Okitsu-Negishi, S., Furusawa, S., Kawa, Y., Hashira, S. Ito, S., Hiruma, F., Mizuguchi, M., Yoshino, K., Abe, T.: "Suppressive effect of intravenous immunoglobulins on the activity of interleukin 1." Immunol. Res.
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「研究成果報告書概要(欧文)」より
