title: 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.
authors.affiliation: Inflammation Program.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Nagao
authors.forename: Reina
authors.initials: R
authors.lastname: Kusunoki
authors.forename: Chiaki
authors.initials: C
authors.lastname: Iwamura
authors.forename: Shigeto
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Wako
authors.initials: W
authors.lastname: Yumura
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kameoka
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D012263:Ribonucleosides / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000906:Antibodies; D019268:Antibodies, Antineutrophil Cytoplasmic; D018932:Chemokine CCL2; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D012263:Ribonucleosides; C010052:mizoribine; D009195:Peroxidase
keywords: Anti-neutrophil cytoplasmic autoantibodies-associated glomerulonephritis; anti-neutrophil cytoplasmic antibody against myeloperoxidase; interleukin-6; mizoribine