PMID- 15170926
OWN - NLM
STAT- MEDLINE
DCOM- 20040914
LR  - 20041117
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 31
IP  - 6
DP  - 2004 Jun
TI  - Anti-interleukin 6 receptor antibody inhibits murine AA-amyloidosis.
PG  - 1132-8
AB  - 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. CONCLUSION: 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.
FAU - Mihara, Masahiko
AU  - Mihara M
AD  - Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Shizuoka, 
      Japan. miharamsh@chugai-pharm.co.jp
FAU - Shiina, Masashi
AU  - Shiina M
FAU - Nishimoto, Norihiro
AU  - Nishimoto N
FAU - Yoshizaki, Kazuyuki
AU  - Yoshizaki K
FAU - Kishimoto, Tadamitsu
AU  - Kishimoto T
FAU - Akamatsu, Ken-Ichi
AU  - Akamatsu K
LA  - eng
PT  - Journal Article
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Serum Amyloid A Protein)
SB  - IM
MH  - Amyloidosis/*immunology/pathology/*therapy
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Disease Models, Animal
MH  - Interleukin-6/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, Interleukin-6/*immunology
MH  - Serum Amyloid A Protein/*immunology
EDAT- 2004/06/02 05:00
MHDA- 2004/09/15 05:00
CRDT- 2004/06/02 05:00
PHST- 2004/06/02 05:00 [pubmed]
PHST- 2004/09/15 05:00 [medline]
PHST- 2004/06/02 05:00 [entrez]
AID - 0315162X-31-1132 [pii]
PST - ppublish
SO  - J Rheumatol. 2004 Jun;31(6):1132-8.