Clinical Relevance of Persistently Elevated Circulating Cytokines (Tumor Necrosis Factor α and Interleukin-6) in the Long-Term Followup of Patients With Giant Cell Arteritis

Objective. To assess the clinical relevance of increased circulating cytokines in patients with giant cell arteritis (GCA) after long-term followup. Methods. We performed a cross-sectional evaluation of 54 patients with biopsy-proven GCA prospectively followed for a median of 5.4 years (range 4-10.5 years). GCA-related complications, vascular events, relapses, current prednisone dose, time required to achieve a maintenance prednisone dosage <10 mg/day, cumulated prednisone at that point, and adverse effects during followup were recorded. Serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) were determined by immunoassay. Results. All patients were in clinical remission. Both cytokines were significantly higher in patients than in controls (mean +/- SD 21 +/- 35 versus 5 +/- 11 pg/ ml; P < 0.001 for IL-6 and mean +/- SD 32 +/- 14 versus 16 +/- 9 pg/ ml; P < 0.001 for TNF alpha). No differences were found in patients with or without GCA-related complications or vascular events during followup. Circulating cytokines were significantly higher in patients who had experienced relapses (mean +/- SD 25 +/- 39 versus 10 +/- 11 pg/ ml; P = 0.04 for IL-6 and mean +/- SD 34 +/- 15 versus 25 +/- 11 pg/ ml; P = 0.042 for TNF alpha). IL-6 was significantly higher in patients still requiring prednisone (mean +/- SD 29 +/- 45 versus 13 +/- 17 pg/ ml; P = 0.008), and TNF alpha correlated with cumulated prednisone dose (r = 0.292, P = 0.04). No significant relationship was found between elevated cytokines and prednisone adverse effects or patients' quality of life. Conclusion. Circulating TNF alpha and IL-6 may persist elevated in GCA patients after long-term followup and remain higher in patients who have experienced more relapsing disease. However, in this patient cohort, elevated circulating cytokines were not associated with increased frequency of GCA complications, vascular events, or treatment-related side effects.