title: Anti-interleukin 6 receptor antibody inhibits murine AA-amyloidosis.
abstract: OBJECTIVE
  AA-amyloidosis is a severe complication in chronic inflammatory diseases. AA-amyloidosis is caused by the deposition of insoluble fibrils containing AA amyloid protein derived from serum amyloid A (SAA), which is synthesized by inflammatory cytokine stimulation. We examined whether anti-interleukin 6 receptor (IL-6R) antibody prevented the development of AA-amyloidosis in mouse models.
  
  
  METHODS
  A transient model was induced by the injection of amyloid enhancing factor (AEF) and adjuvant treatment in C57BL/6 mice. Monoclonal IgG1 antibody, MR16-1, was injected intraperitoneally just once before the injection of AEF and adjuvant. After 2 and 5 weeks, mice were sacrificed and histologically examined. In contrast, a chronic model was induced by AEF injection into IL-6 transgenic mice. One week later, in order to avoid neutralizing antibody production, MR16-1 (200 mg/kg) was injected intravenously. MR16-1 (5 mg/kg) was injected subcutaneously twice a week from the next week. Three and 6 weeks after AEF injection, mice were sacrificed and histologically examined.
  
  
  RESULTS
  In the transient model, amyloid deposition was observed in the spleen, liver, and kidney as early as 2 weeks after treatment. MR16-1 completely prevented amyloid deposition. Although IL-6 production was not suppressed, SAA production was significantly suppressed. In the chronic model, substantial amyloid deposition was seen in multiple organs and tissues as well as the spleen, liver, and kidney. MR16-1 suppressed amyloid deposition in many organs, even when injected one week after AEF injection; it showed a tendency to decrease SAA and IL-6 levels were decreased.
  
  
  CONCLUSIONS
  IL-6 is a key cytokine for the induction of AA-amyloidosis, and anti-IL-6R therapy appears promising for the treatment of AA-amyloidosis.
authors.affiliation: Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan. miharamsh@chugai-pharm.co.jp
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mihara
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiina
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yoshizaki
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Akamatsu
mesh_terms: D000686:Amyloidosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D000685:Serum Amyloid A Protein / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000685:Serum Amyloid A Protein