Seitz M, Dewald B, Gerber N, Baggiolini M
Division of Rheumatology, University Clinic, Inselspital, Bern, Switzerland.
J Clin Invest. 1991 Feb;87(2):463-9. doi: 10.1172/JCI115018.
Production of the neutrophil-activating peptide (NAP)-1/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-8. In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-1/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-8 was 3- to 10-fold higher in PBMC and even much higher in SFMC from RA patients. In all instances, the yield of NAP-1/IL-8 could be enhanced by stimulation in culture. In addition to LPS, rheumatoid factor-containing immune complexes, zymosan, and IL-1 were highly effective in inducing NAP-1/IL-8 production, while IL-3, GM-CSF, tumor necrosis factor (TNF), and IL-2 were somewhat less potent. An inhibitory effect was obtained with IFN-gamma, which significantly decreased the spontaneous NAP-1/IL-8 release from SFMC and the IL-1- and LPS-induced NAP-1/IL-8 from RA and control PBMC. Inhibition was also observed with glucocorticoids. The production of NAP-1/IL-8 was markedly reduced by dexamethasone in phagocytosis-stimulated PBMC, and almost totally inhibited in SFMC obtained from joints after intraarticular administration of betamethasone. By contrast, the cyclooxygenase inhibitor, indomethacin, tended to increase the NAP-1/IL-8 yield from PBMC in culture.
在不同条件下，研究了类风湿关节炎（RA）患者和对照受试者的单核吞噬细胞产生中性粒细胞激活肽（NAP）-1/白细胞介素（IL）-8的情况。将来自骨髓的单核细胞（BMMC）、外周血单核细胞（PBMC）和滑液单核细胞（SFMC）在不存在或存在大肠杆菌脂多糖（LPS）、不同白细胞介素、干扰素-γ、酵母聚糖或免疫复合物的情况下培养长达48小时，并测定释放到培养基中的中性粒细胞刺激活性。用针对人重组NAP-1/IL-8产生的抗血清进行中和试验表明，这种活性的90%以上可归因于NAP-1/IL-8。在未受刺激的对照个体单核细胞和RA患者的BMMC中，NAP-1/IL-8的产生非常低，LPS刺激可使其适度增加。相比之下，RA患者的PBMC中NAP-1/IL-8的自发产生高出3至10倍，在SFMC中甚至更高。在所有情况下，培养中的刺激均可提高NAP-1/IL-8的产量。除LPS外，含类风湿因子的免疫复合物、酵母聚糖和IL-1在诱导NAP-1/IL-8产生方面非常有效，而IL-3、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、肿瘤坏死因子（TNF）和IL-2的效力稍弱。干扰素-γ具有抑制作用，可显著降低SFMC中NAP-1/IL-8的自发释放以及RA和对照PBMC中IL-1和LPS诱导的NAP-1/IL-8释放。糖皮质激素也有抑制作用。地塞米松可使吞噬作用刺激的PBMC中NAP-1/IL-8的产生明显减少，关节内注射倍他米松后从关节获得的SFMC中NAP-1/IL-8几乎完全被抑制。相比之下，环氧化酶抑制剂吲哚美辛倾向于增加培养的PBMC中NAP-1/IL-8的产量。
