title: IK cytokine ameliorates the progression of lupus nephritis in MRL/lpr mice.
abstract: OBJECTIVE
  IK cytokine has been isolated as a factor that inhibits interferon-gamma (IFNgamma)-induced expression of class II major histocompatibility complex (MHC) antigens. Aberrant expression of class II MHC antigens has reportedly been recognized in the target organs of autoimmune diseases and been associated with disease activity. In this study, we investigated whether IK cytokine can ameliorate the progression of lupus nephritis in MRL/lpr mice.
  
  
  METHODS
  A truncated IK analog was prepared and transfected into a nonmetastatic fibroblastoid cell line, and then injected subcutaneously into MRL/lpr mice at ages 8 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease).
  
  
  RESULTS
  An IK cytokine, when it was translated from methionine at position 316, acted as a secretory protein. This truncated IK cytokine (tIK) reduced IFNgamma-induced class II MHC expression in various cells through decreased expression of class II MHC transcription activator. Treatment of MRL/lpr mice with tIK significantly reduced renal damage as compared with control mice. A significant decrease in macrophage and T cell infiltration was found in the kidneys of tIK-treated mice, resulting in decreased production of IFNgamma and interleukin-2. Mice treated with tIK also showed significant reduction of anti-DNA antibodies and circulating immune complexes. A specific reduction of class II MHC expression was observed on B cells and monocytes as well as in the kidney.
  
  
  CONCLUSIONS
  We prepared a potent IK analog and demonstrated its ability to ameliorate the progression of lupus nephritis. This agent may therefore provide a new therapeutic approach for lupus nephritis.
authors.affiliation: Ehime University School of Medicine, Ehime, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Muraoka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Kohno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inoue
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Miho
authors.initials: M
authors.lastname: Terada
authors.forename: Masato
authors.initials: M
authors.lastname: Nose
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D015870:Gene Expression / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007371:Interferon-gamma / Q000097:blood / Q000494:pharmacology; D007376:Interleukin-2 / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000502:physiology; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D013154:Spleen / Q000502:physiology; D014162:Transfection; D014657:Vasculitis / Q000276:immunology / Q000473:pathology / Q000628:therapy
chemical_list: D000974:Antibodies, Antinuclear; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C484250:Ik protein, mouse; D007376:Interleukin-2; D007371:Interferon-gamma