435 De Lauretis, et al: IL-6 predicts survival in SSc-ILD Personal non-commercial use only. The Journal of Rheumatology Copyright © 2013. All rights reserved. Serum Interleukin 6 Is Predictive of Early Functional Decline and Mortality in Interstitial Lung Disease Associated with Systemic Sclerosis Angelo De Lauretis, Piersante Sestini, Panagiotis Pantelidis, Rachel Hoyles, David M. Hansell, Nicole S.L. Goh, Christopher J. Zappala, Dina Visca, Toby M. Maher, Christopher P. Denton, Voon H. Ong, David J. Abraham, Peter Kelleher, Laureen Hector, Athol U. Wells, and Elisabetta A. Renzoni ABSTRACT. 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. (J Rheumatol First Release Feb 1 2013; doi:10.3899/jrheum.120725) Key Indexing Terms: SCLERODERMA PULMONARY FIBROSIS INTERLEUKIN 6 SERUM BIOMARKERS From the Department of Pneumology, Carlo Poma Hospital, Mantua, Italy; Department of Pneumology, Università Cattolica del Sacro Cuore, Rome, Italy; Department of Respiratory Medicine, University of Siena, Ospedale “Le Scotte,” Siena, Italy; Infection and Immunity Laboratory, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK; Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Hospital, London, UK; Department of Radiology, Royal Brompton Hospital, London, UK; Respiratory and Sleep Medicine, Austin Health, Melbourne, Australia; Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; and the Immunology Section, Division of Infectious Diseases, Imperial College, Chelsea and Westminster Hospital, London, UK. Supported by the European Respiratory Society Short-Term Research Fellowship grant ERS-STRF 595 and by the Raynaud’s and Scleroderma Association; and by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. Dr. Sestini was supported by MIUR project no. 2008W7XP29. A. De Lauretis, MD, Department of Pneumology, Carlo Poma Hospital, Department of Pneumology, Università Cattolica del Sacro Cuore; P. Sestini, MD, Department of Respiratory Medicine, University of Siena, Ospedale “Le Scotte”; P. Pantelidis, PhD, Infection and Immunity Laboratory, Imperial College Healthcare NHS Trust, Charing Cross Hospital; R. Hoyles, MD, PhD, Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Hospital; D.M. Hansell, MD, FRCP, FRCR, Department of Radiology, Royal Brompton Hospital; N.S.L. Goh, MD, PhD, Respiratory and Sleep Medicine, Austin Health; C.J. Zappala, MD, FRACP, Interstitial Lung Disease Unit, Royal Brompton Hospital; D. Visca, MD, Department of Pneumology, Università Cattolica del Sacro Cuore; T.M. Maher, MRCP, PhD, Interstitial Lung Disease Unit, Royal Brompton Hospital; C.P. Denton, MD, PhD; V.H. Ong, PhD, MRCP; D.J. Abraham, PhD, Centre for Rheumatology and Connective Tissue Diseases, UCL Medical School, Royal Free Hospital; P. Kelleher, PhD, Infection and Immunity Laboratory, Imperial College Healthcare NHS Trust, Charing Cross Hospital, Immunology Section, Division of Infectious Diseases, Imperial College, Chelsea and Westminster Hospital; L. Hector, BSc, PhD, Infection and Immunity Laboratory, Imperial College Healthcare NHS Trust, Charing Cross Hospital; A.U. Wells, FRACP, MD, FRCP, FRCR; E.A. Renzoni, MD, PhD, Interstitial Lung Disease Unit, Royal Brompton Hospital. Address correspondence to Dr. E. Renzoni, Interstitial Lung Disease Unit, Royal Brompton Hospital, Emmanuel Kaye Building, 1B Manresa Road, London SW3 6LR, UK. E-mail: e.renzoni@imperial.ac.uk Accepted for publication December 4, 2012. Systemic sclerosis (SSc) is an autoimmune condition characterized by tissue fibrosis of the skin and internal organs. Interstitial lung disease associated with SSc (SSc-ILD) accounts for about one-third of deaths 1,2,3 . Clinical variables associated with a higher risk of progression of SSc-ILD include severity of lung www.jrheum.org Downloaded on January 20, 2022 from