PMID- 11285378
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20220409
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 40
IP  - 3
DP  - 2001 Mar
TI  - Expression of interleukin-18 and its monokine-directed function in rheumatoid 
      arthritis.
PG  - 302-9
AB  - OBJECTIVES: To investigate the expression of and monokine induction by 
      interleukin 18 (IL-18; also called interferon-gamma inducing factor, IGIF), in 
      peripheral blood mononuclear cells (PBMC) and cultured synoviocytes from 
      rheumatoid arthritis (RA) patients. METHODS: We carried out IL-18 Western 
      blotting and semi-quantitative reverse transcription-polymerase chain reaction 
      (RT-PCR) of cytokines in PBMC [IL-18, IL-1beta and tumour necrosis factor alpha 
      (TNF-alpha)] and long-term cultured fibroblast-like synoviocytes (FLS) [IL-18, 
      IL-1beta, TNF-alpha, IL-6, interferon gamma (INF-gamma) and 
      [granulocyte-macrophage colony stimulating factor (GM-CSF)] from RA patients and 
      controls. FLS were isolated from RA synovial membranes (FLS(SM)) and RA synovial 
      fluids (FLS(SF)), osteoarthritis (OA) FLS(SM) and FLS(SF) from 
      spondyloarthropathy patients. FLS were characterized by fluorescence-activated 
      cell sorting of the FLS. PBMC and FLS from RA patients and control subjects were 
      stimulated with recombinant human IL-18 and IL-1beta (rHuIL-18/rHuIL-1beta), and 
      TNF-alpha, IL-1beta and MMP-1 were measured by ELISA in supernatants. RESULTS: 
      Constitutive expression of IL-18 mRNA was significantly reduced whereas that of 
      TNF-alpha was enhanced in RA PBMC. Persistent low expression of IL-18, TNF-alpha, 
      GM-CSF and IL-1beta was observed in RA and OA FLS(SM) as well as 
      spondyloarthropathy FLS(SF). In contrast, high constitutive expression of IL-18 
      in FLS (CD90/Thy-1- and CD54-positive, CD14- and CD86-negative), accompanied by 
      persistent high levels of TNF-alpha, GM-CSF and IL-1beta expression, was 
      restricted to synovial fluid-derived FLS obtained from RA patients. IFN-gamma was 
      not detectable in any culture, but IL-6 mRNA was equally expressed in all FLS 
      cultures. rHuIL-18 was effective in stimulating TNF-alpha and IL-1beta secretion 
      in PBMC from healthy controls, but failed to stimulate TNF-alpha and IL-1beta 
      secretion from PBMC in 11 of 12 RA patients, and all FLS cultures. rHu-IL-1beta, 
      but not rHu-IL-18, induced interstitial collagenase (MMP-1) in FLS. CONCLUSIONS: 
      Persistent high production of proinflammatory cytokines in RA-FLS(SF) may be 
      relevant for chronic progression in RA synovitis. Levels of TNF-alpha and 
      IL-1beta expression are increased in RA-FLS(SF), but are independent of IL-18. 
      The pathological function of enhanced IL-18 expression in RA-FLS(SF) remains to 
      be further elucidated.
FAU - Moller, B
AU  - Moller B
AD  - Centre for Rheumatic Diseases, Department of Internal Medicine, University 
      Hospital Frankfurt, Germany.
FAU - Kukoc-Zivojnov, N
AU  - Kukoc-Zivojnov N
FAU - Kessler, U
AU  - Kessler U
FAU - Rehart, S
AU  - Rehart S
FAU - Kaltwasser, J P
AU  - Kaltwasser JP
FAU - Hoelzer, D
AU  - Hoelzer D
FAU - Kalina, U
AU  - Kalina U
FAU - Ottmann, O G
AU  - Ottmann OG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Interleukin-18)
RN  - 0 (Monokines)
SB  - IM
MH  - Adult
MH  - Arthritis, Rheumatoid/*blood/*immunology
MH  - Cells, Cultured/immunology
MH  - Female
MH  - Humans
MH  - Interleukin-18/*blood/*immunology
MH  - Leukocytes, Mononuclear/immunology
MH  - Male
MH  - Middle Aged
MH  - Monokines/blood/*immunology
MH  - Synovial Membrane/immunology
MH  - Time Factors
EDAT- 2001/04/04 10:00
MHDA- 2001/05/22 10:01
CRDT- 2001/04/04 10:00
PHST- 2001/04/04 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/04 10:00 [entrez]
AID - 10.1093/rheumatology/40.3.302 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2001 Mar;40(3):302-9. doi: 10.1093/rheumatology/40.3.302.