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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.

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.
AuthorsTomokazu Nagao, Reina Kusunoki, Chiaki Iwamura, Shigeto Kobayashi, Wako Yumura, Yosuke Kameoka, Toshinori Nakayama, Kazuo Suzuki
JournalMicrobiology and immunology (Microbiol Immunol) Vol. 57 Issue 9 Pg. 640-50 (Sep 2013) ISSN: 1348-0421 [Electronic] Australia
PMID23829825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 The Societies and Wiley Publishing Asia Pty Ltd.
Chemical References
  • Antibodies
  • Antibodies, Antineutrophil Cytoplasmic
  • Chemokine CCL2
  • Interleukin-6
  • Receptors, Interleukin-6
  • Ribonucleosides
  • mizoribine
  • Peroxidase
Topics
  • Animals
  • Antibodies (administration & dosage)
  • Antibodies, Antineutrophil Cytoplasmic (immunology)
  • Chemokine CCL2 (blood)
  • Disease Models, Animal
  • Female
  • Glomerulonephritis (blood, drug therapy, immunology)
  • Humans
  • Interleukin-6 (blood)
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase (immunology)
  • Receptors, Interleukin-6 (immunology)
  • Ribonucleosides (administration & dosage)
  • T-Lymphocyte Subsets (immunology)

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