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

Objective. To explore the role of proinflammatory cytokines in giant c ell arteritis (GCA) and polymyalgia rheumatica (PMR), two clinically r elated 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 i n plasma IL-6 levels with clinical symptoms during corticosteroid ther apy. Methods. IL-6 and TNFalpha concentrations were determined in plas ma samples from patients with untreated PMR or GCA, and plasma IL-6 le vels were monitored in patients receiving long-term therapy (14 months ) with corticosteroids. To identify IL-6-producing cells, the polymera se chain reaction was used to detect IL-6 messenger RNA. In vitro prod uction of IL-6 and IL-2 by peripheral blood mononuclear cells (PBMC) f rom treated and untreated patients was quantified using IL-6- and IL-2 -specific bioassay systems. Results. IL-6 concentrations were increase d in PMR and GCA patients, whereas TNFalpha concentrations were simila r to those in normal donors. Administration of corticosteroids rapidly reduced the levels of circulating IL-6 but did not correct the underl ying mechanism inducing the increased IL-6 production. In individual p atients, changes in plasma IL-6 levels and clinical manifestations dur ing prolonged therapy were closely correlated. Short-term withdrawal o f corticosteroids, even after several months of treatment, was followe d by an immediate increase in plasma IL-6 concentrations. To identify the cellular source of plasma IL-6, PBMC from treated and untreated pa tients 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 exclusiv ely from CD14+ cells. Conclusion. Increased production of IL-6, but no t TNFalpha, is a characteristic finding in patients with PMR or GCA. C orticosteroids rapidly suppress IL-6 production but do not correct the underlying mechanism inducing the increased IL-6 production. The clos e correlation of plasma IL-6 concentrations with clinical symptoms sug gests a direct contribution of this cytokine to the disease manifestat ions and presents the possibility that monitoring IL-6 levels would be useful in making decisions on adjustment of corticosteroid dosage in individual patients.