TY - JOUR T1 - Serum Interleukin 6 Is Predictive of Early Functional Decline and Mortality in Interstitial Lung Disease Associated with Systemic Sclerosis JF - The Journal of Rheumatology JO - J Rheumatol SP - 435 LP - 446 DO - 10.3899/jrheum.120725 VL - 40 IS - 4 AU - Angelo De Lauretis AU - Piersante Sestini AU - Panagiotis Pantelidis AU - Rachel Hoyles AU - David M. Hansell AU - Nicole S.L. Goh AU - Christopher J. Zappala AU - Dina Visca AU - Toby M. Maher AU - Christopher P. Denton AU - Voon H. Ong AU - David J. Abraham AU - Peter Kelleher AU - Laureen Hector AU - Athol U. Wells AU - Elisabetta A. Renzoni Y1 - 2013/04/01 UR - http://www.jrheum.org/content/40/4/435.abstract N2 - Objective. Biomarkers of progression of interstitial lung disease (ILD) are needed to allow early therapeutic intervention in patients with scleroderma-associated disease (SSc-ILD). Methods. A panel of 8 serum cytokines [interleukin 6 (IL-6), IL-8, IL-10, CCL2, CXCL10, vascular endothelial growth factor, fibroblast growth factor 2, and CX3CL1] was assessed by Luminex bead technology in exploratory cohorts of 74 patients with SSc and 58 patients with idiopathic pulmonary fibrosis (IPF). Mortality and significant lung function decline [forced vital capacity (FVC) ≥ 10%; DLCO ≥ 15%] from date of serum collection were evaluated by proportional hazards analysis. Based on these findings, the prognostic value of serum IL-6, evaluated by ELISA, was assessed in a larger test cohort of 212 patients with SSc-ILD. Results. In the exploratory cohort, only serum IL-6 was an independent predictor of DLCO decline in both IPF and SSc-ILD. The IL-6 threshold level most predictive of DLCO decline within a year was 7.67 pg/ml. In the larger test cohort, serum IL-6 > 7.67 pg/ml was predictive of decline in FVC (HR 2.58 ± 0.98, p = 0.01) and in DLCO (HR 3.2 ± 1.7, p = 0.02) within the first year, and predictive of death within the first 30 months (HR 2.69 ± 0.96, p = 0.005). When stratified according to severity (FVC < 70%), serum IL-6 > 7.67 pg/ml was predictive of functional decline or death within the first year in patients with milder disease (OR 3.1, 95% CI 1.4–7.2, p = 0.007), but not in those with severe ILD. Conclusion. In SSc-ILD, serum IL-6 levels appear to be predictive of early disease progression in patients with mild ILD, and could be used to target treatment in this group, if confirmed by prospective studies. ER -