PMID- 11263769
OWN - NLM
STAT- MEDLINE
DCOM- 20010503
LR  - 20220408
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 44
IP  - 3
DP  - 2001 Mar
TI  - Levels of interleukin-18 and its binding inhibitors in the blood circulation of 
      patients with adult-onset Still's disease.
PG  - 550-60
AB  - OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine that is involved 
      in immunologically mediated tissue damage, but its bioactivity is regulated in 
      vivo by its soluble decoy receptor, IL-18 binding protein (IL-18BP). This study 
      was undertaken to determine levels of IL-18 and IL-18 binding inhibition in the 
      blood of patients with adult-onset Still's disease (ASD). METHODS: Serum 
      concentrations of IL-18 in ASD patients were compared by enzyme-linked 
      immunosorbent assay (ELISA) with those in patients with other systemic rheumatic 
      diseases and healthy controls. The biologically active mature protein of IL-18 
      was detected by Western blot analysis with anti-IL-18 antibody and its induction 
      of interferon-gamma (IFNgamma) secretion from IL-18-responding human 
      myelomonocytic KG-1 cells. The inhibitory activity on IL-18 binding to its 
      receptor was determined by 125I-IL-18 binding inhibition assay using the Chinese 
      hamster ovary cell line transfected with a murine IL-18 receptor 
      (CHO-K1/mIL-18R). RESULTS: Concentrations of serum IL-18 were extremely elevated 
      in patients with active ASD compared with those in patients with rheumatoid 
      arthritis, systemic lupus erythematosus, systemic sclerosis, 
      polymyositis/dermatomyositis, Sjogren's syndrome, or healthy individuals. Levels 
      of IL-18 were found to correlate with serum ferritin values and disease severity 
      in ASD. Western blot analysis revealed that serum samples from patients with 
      active ASD contained an 18-kd polypeptide of IL-18, corresponding in size to the 
      mature form. Accordingly, the samples were able to induce IFNgamma secretion from 
      KG-1 cells, which was largely abolished by neutralizing anti-IL-18 antibody. 
      However, the level of IL-18 bioactivity was more than 10-fold weaker than the 
      concentration of IL-18 protein measured by ELISA. Serum samples from patients 
      with active ASD showed an inhibitory effect on the binding of 125I-IL-18 to 
      CHO-K1/mIL-18R cells, and this activity was associated with elevation of IL-18. 
      CONCLUSION: These data indicate that systemic overproduction of IL-18 may be 
      closely related to the pathogenesis of ASD, despite the restriction on its 
      inflammatory activity by IL-18 binding inhibitors such as IL-18BP. The disease 
      activity appears to be determined on the basis of the relative levels of IL-18 
      and its specific inhibitors.
FAU - Kawashima, M
AU  - Kawashima M
AD  - Okayama University Medical School, Japan.
FAU - Yamamura, M
AU  - Yamamura M
FAU - Taniai, M
AU  - Taniai M
FAU - Yamauchi, H
AU  - Yamauchi H
FAU - Tanimoto, T
AU  - Tanimoto T
FAU - Kurimoto, M
AU  - Kurimoto M
FAU - Miyawaki, S
AU  - Miyawaki S
FAU - Amano, T
AU  - Amano T
FAU - Takeuchi, T
AU  - Takeuchi T
FAU - Makino, H
AU  - Makino H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-18)
RN  - 0 (RNA, Messenger)
RN  - 0 (interleukin-18 binding protein)
SB  - IM
CIN - Arthritis Rheum. 2002 Sep;46(9):2539-41; author reply 2541-2. PMID: 12355506
MH  - Adult
MH  - Arthritis, Rheumatoid/blood
MH  - Blood Circulation
MH  - Female
MH  - Gene Expression
MH  - Glycoproteins/*antagonists & inhibitors/*blood
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Interleukin-18/blood/genetics
MH  - Male
MH  - Monocytes/chemistry
MH  - RNA, Messenger/blood
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Still's Disease, Adult-Onset/*blood
EDAT- 2001/03/27 10:00
MHDA- 2001/05/05 10:01
CRDT- 2001/03/27 10:00
PHST- 2001/03/27 10:00 [pubmed]
PHST- 2001/05/05 10:01 [medline]
PHST- 2001/03/27 10:00 [entrez]
AID - 10.1002/1529-0131(200103)44:3<550::AID-ANR103>3.0.CO;2-5 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2001 Mar;44(3):550-60. doi: 
      10.1002/1529-0131(200103)44:3<550::AID-ANR103>3.0.CO;2-5.