Expression of interleukin-18 and its monokine-directed function in rheumatoid arthritis

被引:36
作者
Möller, B
Kukoc-Zivojnov, N
Kessler, U
Rehart, S
Kaltwasser, JP
Hoelzer, D
Kalina, U
Ottmann, OG
机构
[1] Univ Frankfurt Klinikum, Med Klin 3, Ctr Rheumat Dis, Lab B2 19 20, D-64686 Lautertal, Germany
[2] Univ Frankfurt Klinikum, Dept Internal Med, D-64686 Lautertal, Germany
[3] Univ Frankfurt Klinikum, Dept Arthrit Surg, D-64686 Lautertal, Germany
关键词
rheumatoid arthritis; IL-18; fibroblast-like synoviocytes; PBMC; cytokines;
D O I
10.1093/rheumatology/40.3.302
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-1 beta and tumour necrosis factor alpha (TNF-alpha)] and long-term cultured fibroblast-like synoviocytes (FLS) [IL-18, IL-1 beta, 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 (FLSSM) and RA synovial fluids (FLSSF), osteoarthritis (OA) FLSSM and FLSSF: 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-1 beta (rHuIL-18/rHuIL-1 beta), and TNF-alpha, IL-1 beta 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-1 beta was observed in RA and OA FLSSM as well as spondyloarthropathy FLSSF. 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-1 beta 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-1 beta secretion in PBMC from healthy controls, but failed to stimulate TNF-alpha and IL-1 beta secretion from PBMC in 11 of 12 RA patients, and all FLS cultures. rHu-IL-1 beta, but not rHu-IL-18, induced interstitial collagenase (MMP-1) in FLS. Conclusions. Persistent high production of proinflammatory cytokines in RA-FLSSF may be relevant for chronic progression in RA synovitis. Levels of TNF-alpha and IL-1 beta expression are increased in RA-FLSSF, but are independent of IL-18. The pathological function of enhanced IL-18 expression in RA-FLSSF remains to be further elucidated.
引用
收藏
页码:302 / 309
页数:8
相关论文
共 31 条
  • [1] Ahn HJ, 1997, J IMMUNOL, V159, P2125
  • [2] THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS
    ARNETT, FC
    EDWORTHY, SM
    BLOCH, DA
    MCSHANE, DJ
    FRIES, JF
    COOPER, NS
    HEALEY, LA
    KAPLAN, SR
    LIANG, MH
    LUTHRA, HS
    MEDSGER, TA
    MITCHELL, DM
    NEUSTADT, DH
    PINALS, RS
    SCHALLER, JG
    SHARP, JT
    WILDER, RL
    HUNDER, GG
    [J]. ARTHRITIS AND RHEUMATISM, 1988, 31 (03): : 315 - 324
  • [3] Burger D, 1998, ARTHRITIS RHEUM, V41, P1748, DOI 10.1002/1529-0131(199810)41:10<1748::AID-ART7>3.3.CO
  • [4] 2-V
  • [5] Mononuclear phagocytes and rheumatoid synovitis - Mastermind or workhorse in arthritis?
    Burmester, GR
    Stuhlmuller, B
    Keyszer, G
    Kinne, RW
    [J]. ARTHRITIS AND RHEUMATISM, 1997, 40 (01): : 5 - 18
  • [6] Chen V, 1998, BRIT J RHEUMATOL, V37, P148
  • [7] Overview of interleukin-18:: more than an interferon-γ inducing factor
    Dinarello, CA
    Novick, D
    Puren, AJ
    Fantuzzi, G
    Shapiro, L
    Mühl, H
    Yoon, DY
    Reznikov, LL
    Kim, SH
    Rubinstein, M
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1998, 63 (06) : 658 - 664
  • [8] Biologic basis for interleukin-1 in disease
    Dinarello, CA
    [J]. BLOOD, 1996, 87 (06) : 2095 - 2147
  • [9] THE EUROPEAN-SPONDYLARTHROPATHY-STUDY-GROUP PRELIMINARY CRITERIA FOR THE CLASSIFICATION OF SPONDYLARTHROPATHY
    DOUGADOS, M
    VANDERLINDEN, S
    JUHLIN, R
    HUITFELDT, B
    AMOR, B
    CALIN, A
    CATS, A
    DIJKMANS, B
    OLIVIERI, I
    PASERO, G
    VEYS, E
    ZEIDLER, H
    [J]. ARTHRITIS AND RHEUMATISM, 1991, 34 (10): : 1218 - 1227
  • [10] Feldmann M, 1998, SPRINGER SEMIN IMMUN, V20, P211, DOI 10.1007/BF00832008