Roche N E, Fulbright J W, Wagner A D, Hunder G G, Goronzy J J, Weyand C M
Department of Medicine, Mayo Clinic, Rochester, MN 55905.
Arthritis Rheum. 1993 Sep;36(9):1286-94. doi: 10.1002/art.1780360913.
To explore the role of proinflammatory cytokines in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), two clinically related syndromes characterized by an intense acute-phase reaction. In particular, to determine plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) and to correlate changes in plasma IL-6 levels with clinical symptoms during corticosteroid therapy.
IL-6 and TNF alpha concentrations were determined in plasma samples from patients with untreated PMR or GCA, and plasma IL-6 levels were monitored in patients receiving long-term therapy (14 months) with corticosteroids. To identify IL-6-producing cells, the polymerase chain reaction was used to detect IL-6 messenger RNA. In vitro production of IL-6 and IL-2 by peripheral blood mononuclear cells (PBMC) from treated and untreated patients was quantified using IL-6- and IL-2-specific bioassay systems.
IL-6 concentrations were increased in PMR and GCA patients, whereas TNF alpha concentrations were similar to those in normal donors. Administration of corticosteroids rapidly reduced the levels of circulating IL-6 but did not correct the underlying mechanism inducing the increased IL-6 production. In individual patients, changes in plasma IL-6 levels and clinical manifestations during prolonged therapy were closely correlated. Short-term withdrawal of corticosteroids, even after several months of treatment, was followed by an immediate increase in plasma IL-6 concentrations. To identify the cellular source of plasma IL-6, PBMC from treated and untreated patients with PMR or GCA were analyzed for their ability to secrete IL-6 and the T cell-specific cytokine IL-2. Polyclonal T cell stimulation caused a rapid release of IL-6, which was shown to be derived exclusively from CD14+ cells.
Increased production of IL-6, but not TNF alpha, is a characteristic finding in patients with PMR or GCA. Corticosteroids rapidly suppress IL-6 production but do not correct the underlying mechanism inducing the increased IL-6 production. The close correlation of plasma IL-6 concentrations with clinical symptoms suggests a direct contribution of this cytokine to the disease manifestations and presents the possibility that monitoring IL-6 levels would be useful in making decisions on adjustment of corticosteroid dosage in individual patients.
探讨促炎细胞因子在巨细胞动脉炎（GCA）和风湿性多肌痛（PMR）中的作用，这两种临床相关综合征的特征是强烈的急性期反应。特别是要测定白细胞介素-6（IL-6）和肿瘤坏死因子α（TNFα）的血浆浓度，并将血浆IL-6水平的变化与皮质类固醇治疗期间的临床症状相关联。
测定未经治疗的PMR或GCA患者血浆样本中的IL-6和TNFα浓度，并监测接受皮质类固醇长期治疗（14个月）患者的血浆IL-6水平。为了鉴定产生IL-6的细胞，使用聚合酶链反应检测IL-6信使核糖核酸。使用IL-6和IL-2特异性生物测定系统对来自治疗和未治疗患者的外周血单个核细胞（PBMC）体外产生IL-6和IL-2的情况进行定量。
PMR和GCA患者的IL-6浓度升高，而TNFα浓度与正常供体相似。给予皮质类固醇迅速降低循环IL-6水平，但未纠正诱导IL-6产生增加的潜在机制。在个体患者中，长期治疗期间血浆IL-6水平的变化与临床表现密切相关。即使在治疗数月后短期停用皮质类固醇，随后血浆IL-6浓度也会立即升高。为了鉴定血浆IL-6的细胞来源，分析了来自治疗和未治疗的PMR或GCA患者的PBMC分泌IL-6和T细胞特异性细胞因子IL-2的能力。多克隆T细胞刺激导致IL-6迅速释放，结果表明其仅来源于CD14+细胞。
IL-6产生增加而非TNFα产生增加是PMR或GCA患者的特征性发现。皮质类固醇迅速抑制IL-6产生，但未纠正诱导IL-6产生增加的潜在机制。血浆IL-6浓度与临床症状的密切相关性表明该细胞因子对疾病表现有直接作用，并提示监测IL-6水平可能有助于对个体患者调整皮质类固醇剂量做出决策。
