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Proinflammatory Cytokine Profiles in Sera and Pathological Tissues of Patients with Active Untreated Adult Onset Still's Disease
DER-YUAN CHEN, JOUNG-LIANG LAN, FANG-JU LIN, and TSU-YI HSIEH
ABSTRACT. Methods. We measured serum levels of interleukin 6 (IL-6), IL-8, and tumor necrosis factor (TNF-a) by immunochemiluminescence method and serum IL-18 levels by ELISA in 50 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. Multivariate analysis was used to evaluate the correlation between serum cytokine levels and disease activity and clinical features of AOSD. We also evaluated the expression of cytokine transcripts by real-time quantitative polymerase chain reaction in biopsy specimens of evanescent rash and synovitis from 12 patients with active untreated AOSD. Results. Significantly higher levels of IL-6, IL-8, IL-18, and TNF-a in sera were found in patients with active untreated AOSD compared to healthy controls. Serum levels of IL-6 and IL-18 correlated well with clinical activity score of AOSD patients. Multiple logistic regression analysis showed that serum IL-6 level was a possible predictor for the occurrence of evanescent rash (p = 0.0593), serum IL-8 level was a significant predictor of persistent arthritis, and serum IL-18 level predicted occurrence of liver dysfunction. The levels of mRNA expression of IL-6, IL-18, and IL-8 were significantly higher in the biopsy tissue of Still's rash from AOSD patients compared with those in controls. Levels of mRNA expression of IL-18, IL-8, and TNF-a were significantly higher in the synovial membranes of AOSD patients compared with those in osteoarthritis controls. Significantly lower levels of TNF-a and IL-8 were found in the sera and in the synovial membranes of AOSD patients compared with those in RA patients. AOSD patients who had a chronic articular course had significantly higher levels of serum IL-8 compared with those who had a monocyclic systemic course. Conclusion. Significantly higher levels of IL-6, IL-8, IL-18, and TNF-a were seen in both sera and pathological tissues of patients with active AOSD. The associations between levels of cytokine profile and distinct clinical manifestations and various patterns of disease course suggest the heterogeneity of pathogenesis in AOSD. (J Rheumatol 2004;31:2189-98) Key Indexing Terms:
ADULT ONSET STILL'S DISEASE
From the Institute of Clinical Medicine, National Yang-Ming University; Department of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital; and School of Medicine, Taipei Medical University, Taipei, Taiwan. Supported by a grant from the Taichung Veterans General Hospital (TCVGH-913803B). D-Y. Chen, MD, Chief, Department of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital; J-L. Lan, MD, Associate Professor of Internal Medicine, Chief of Internal Medicine, Taichung Veterans General Hospital; T-Y. Hsieh, MD, Visiting Doctor; F-J. Lin, MS, Department of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital. Address reprint requests to Dr. J-L. Lan, Department of Internal Medicine, Taichung Veterans General Hospital, No. 160, Section 3, Taichung-Kang Road, Taichung City, 40705, Taiwan. E-mail: jllan@vghtc.gov.tw Submitted November 5, 2003; revision accepted May 19, 2004. |