Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis.
Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis.
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DOI：
10.1084/jem.168.5.1573
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发表时间：
1988-11-01
期刊：
影响因子：
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通讯作者：
Zvaifler NJ
中科院分区：
文献类型：
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作者：
Firestein GS;Xu WD;Townsend K;Broide D;Alvaro-Gracia J;Glasebrook A;Zvaifler NJ
由于以前的研究表明类风湿关节炎(RA)滑液(SF)和滑膜组织(ST)外植体上清液中有低水平的干扰素-γ，我们检测了RA、SF和ST的IL-2和IL-3样活性。在IL-2依赖的小鼠CTLL系中，14个RA SF中有6个导致胸腺嘧啶核苷摄取增加(超过对照的3倍)。其活性不同于IL-2，因为它不被IL-2-R抗体阻断。此外，16例关节标本中未检测到IL-2(<50pg/ml)。用两种检测小鼠IL-3(肥大细胞增殖和骨髓CSF)的方法检测多集落刺激因子(CSF)活性。在肥大细胞测定中，[~3H]TdR摄取率在培养液中为493+/-67cpm，在RA SF存在时为2,910+/-329cpm(p<0.001)，在血清阴性脊柱关节病患者中为1,246+/-156cpm(p<0.001)，在骨性关节炎SF存在时为736+/-100cpm(p>0.10)。在脑脊液检测中，5个RA SF中的4个和5个RA ST中的5个诱导骨髓非贴壁细胞形成集落。巨噬细胞集落最常见，但偶尔也可见混合集落和粒细胞。RA患者的多种CSF活性与IL-3无关，因为人rIL-3在两种小鼠实验中均无活性，且在RA滑膜中未检测到IL-3mRNA。对RA SF的Sephadex柱层析显示，肥大细胞生长因子(约6×10(3)molwt)和脑脊液(约40和100×10(3)molwt)是不同的。RA SF的“类IL-3”活性的集落刺激方面可能是由于CSF-1，因为它是合适的分子质量，并且其活性被特异性的抗-CSF-1抗体中和。最后，RIA检测到RA、SF和ST中的CSF-1含量为1.6-25 ng/ml，在所测试的5个RA滑膜组织中有4个检测到了CSF-1mRNA。
Because previous studies showed low levels of IFN-gamma in rheumatoid arthritis (RA) synovial fluid (SF) and synovial tissue (ST) explant supernatants, we assayed RA SF and ST for IL-2 and IL-3-like activity. Using an IL-2 dependent murine CTLL line, 6 of 14 RA SF caused increased thymidine uptake (greater than three times control). The activity was distinct from IL-2 because it was not blocked by antibody to IL-2-R. In addition, IL-2 was not detected (less than 50 pg/ml) in 16 joint samples using an ELISA. Multi-colony-stimulating factor (CSF) activity was measured using two assays that can detect murine IL-3 (mast cell proliferation, and bone marrow CSF). In the mast cell assay, [3H]TdR uptake was 493 +/- 67 cpm for medium, 2,910 +/- 329 cpm in the presence of RA SF (p less than 0.001), 1,246 +/- 156 cpm in the presence of SF from patients with seronegative spondyloarthropathies (p less than 0.001), and 736 +/- 100 cpm in the presence of osteoarthritis SF (p greater than 0.1). In the CSF assay, four of five RA SF and five of five RA ST induced colony formation from bone marrow nonadherent cells. Macrophage colonies were most common, although mixed colonies and granulocytes were occasionally observed. The multi-CSF activity in RA is not due to IL-3 since human rIL-3 was not active in either murine assay, and IL-3 mRNA was not detected in RA synovium. Sephadex column chromatography of RA SF revealed that the mast cell growth factor (approximately 6 x 10(3) mol wt) and the CSF (approximately 40 and 100 x 10(3) mol wt) are distinct. The colony-stimulating aspect of the "IL- 3-like" activity in RA SF is likely due to CSF-1 because it is the appropriate mol wt and because the activity was neutralized by specific anti-CSF-1 antibody. Finally, an RIA detected 1.6-25 ng/ml of CSF-1 in RA SF and ST and CSF-1 mRNA was detected in four of five RA synovial tissue samples tested.