Correlation of interleukin‐6 and monocyte chemotactic protein‐1 concentrations with crescent formation and myeloperoxidase‐specific anti‐neutrophil cytoplasmic antibody titer in SCG/Kj mice by treatment with anti‐interleukin‐6 receptor antibody or mizoribine |
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Authors: | Tomokazu Nagao Reina Kusunoki Chiaki Iwamura Shigeto Kobayashi Wako Yumura Yosuke Kameoka Toshinori Nakayama Kazuo Suzuki |
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Institution: | 1. Inflammation Program;2. Department of Immunology, Chiba University Graduate School of Medicine, , Chuo‐ku, Chiba, 260‐8670;3. Department of Nephrology, International University of Health and Welfare Hospital, , Nasu‐Shiobara City, Tochigi, 329‐2763;4. Department of Internal Medicine, Juntendo University Koshigaya Hospital, , Koshigaya City, Saitama, 343‐0032;5. Department of Immunology, Tokyo University of Pharmacy and Life Sciences, , Tokyo, 192‐0392;6. Asia International Institute of Infectious Disease Control, Teikyo University, Department of Health Protection, Graduate School of Medicine, , Tokyo, 173‐8605 Japan |
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Abstract: | Myeloperoxidase‐specific anti‐neutrophil cytoplasmic antibody (MPO–ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) and glomerular crescent formation. Pathogenic factors in RPGN were analyzed by using SCG/Kj mice, which spontaneously develop MPO–ANCA‐associated RPGN. The serum concentration of soluble IL‐6R was determined by using ELISA and those of another 23 cytokines and chemokines by Bio‐Plex analysis. Sections of frozen kidney tissue were examined by fluorescence microscopy and the CD3+B220+ T cell subset in the spleen determined by a flow cytometry. Concentrations of IL‐6 and monocyte chemotactic protein‐1 were significantly correlated with the percentages of crescent formation. Anti‐IL‐6R antibody, which has been effective in patients with rheumatoid arthritis, was administered to SCG/Kj mice to elucidate the role of IL‐6 in the development of RPGN. MPO–ANCA titers decreased after administration of anti‐IL‐6R antibody, but not titers of mizoribine, which is effective in Kawasaki disease model mice. These results suggest that IL‐6‐mediated signaling is involved in the production of MPO–ANCA. |
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Keywords: | Anti‐neutrophil cytoplasmic autoantibodies‐associated glomerulonephritis interleukin‐6 anti‐neutrophil cytoplasmic antibody against myeloperoxidase mizoribine |
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