title: Prevention of immune nephritis by the small molecular weight immunomodulator iguratimod in MRL/lpr mice.
abstract: OBJECTIVE
  This study was performed to investigate the therapeutic effects of iguratimod in a lupus mouse model.
  
  
  METHODS
  Female MRL/lpr mice were treated with iguratimod, vehicle solution or cyclophosphamide. Proteinuria was monitored and kidney injury was blindly scored by a renal pathologist. Serum anti-double-stranded DNA antibodies were monitored by radioimmunoassay. Kidney IgG and CD20 were stained by immunohistochemistry. Splenic lymphocyte phenotypes were analyzed by flow cytometry. BAFF, IL-17A, IL-6, and IL-21 levels in serum and splenic lymphocytes were detected by ELISA or quantitative PCR.
  
  
  RESULTS
  Compared with the vehicle-treated controls, MRL/lpr mice treated with iguratimod showed less protenuria, less acute pathological lesions and no chronic changes in the kidneys. There were significant differences in glomerular injury and vasculitis scores, as well as in the semi-quantitative analysis of immune complex deposition between the two groups. Disease activity markers in sera (anti-dsDNA antibodies and immunoglobulin levels) were reduced and hypocomplementemia was attenuated. Lymphocyte expression of BAFF, IL-6, IL-17A and IL-21 was decreased. The abnormal splenic B220+ T cell and plasma cell populations in MRL/lpr mice were reduced by iguratimod treatment, with recovery of the total B cell population and inhibition of B cell infiltration of the kidney tissue. The dosage of iguratimod used in this study showed no significant cytotoxic effects in vivo and no overt side-effects were observed.
  
  
  CONCLUSIONS
  Iguratimod ameliorates immune nephritis in MRL/lpr mice via a non-antiproliferative mechanism. Our data suggest a potential therapeutic role of iguratimod in lupus.
authors.affiliation: Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: Qingran
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: Xinfang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.affiliation: Institute of Health Science, Shanghai Institute for Biological Science, Chinese Academy of Science and Shanghai Jiaotong University School of Medicine, Laboratory of Molecular Rheumatology, Shanghai, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Dai
authors.affiliation: Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Institute of Rheumatology, Shanghai, China.
authors.forename: Chunde
authors.initials: C
authors.lastname: Bao
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002867:Chromones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008970:Molecular Weight; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D002867:Chromones; D016207:Cytokines; D007155:Immunologic Factors; D013449:Sulfonamides; C519076:iguratimod