CORRELATION OF INTERLEUKIN-6 PRODUCTION AND DISEASE-ACTIVITY IN POLYMYALGIA-RHEUMATICA AND GIANT-CELL ARTERITIS

被引:293
作者
ROCHE, NE [1 ]
FULBRIGHT, JW [1 ]
WAGNER, AD [1 ]
HUNDER, GG [1 ]
GORONZY, JJ [1 ]
WEYAND, CM [1 ]
机构
[1] MAYO CLIN & MAYO FDN,DEPT MED,DIV RHEUMATOL,401 GUGGENHEIM BLDG,200 1ST ST SW,ROCHESTER,MN 55905
来源
ARTHRITIS AND RHEUMATISM | 1993年 / 36卷 / 09期
关键词
D O I
10.1002/art.1780360913
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. 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 (TNFalpha) and to correlate changes in plasma IL-6 levels with clinical symptoms during corticosteroid therapy. Methods. IL-6 and TNFalpha 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. Results. IL-6 concentrations were increased in PMR and GCA patients, whereas TNFalpha 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. Conclusion. Increased production of IL-6, but not TNFalpha, 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.
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页码:1286 / 1294
页数:9
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