title: Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pneumology, Carlo Poma Hospital, Mantua, Italy.
authors: Angelo
authors: A
authors: De Lauretis
authors: Piersante
authors: P
authors: Sestini
authors: Panagiotis
authors: P
authors: Pantelidis
authors: Rachel
authors: R
authors: Hoyles
authors: David M
authors: DM
authors: Hansell
authors: Nicole S L
authors: NS
authors: Goh
authors: Christopher J
authors: CJ
authors: Zappala
authors: Dina
authors: D
authors: Visca
authors: Toby M
authors: TM
authors: Maher
authors: Christopher P
authors: CP
authors: Denton
authors: Voon H
authors: VH
authors: Ong
authors: David J
authors: DJ
authors: Abraham
authors: Peter
authors: P
authors: Kelleher
authors: Laureen
authors: L
authors: Hector
authors: Athol U
authors: AU
authors: Wells
authors: Elisabetta A
authors: EA
authors: Renzoni
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000097:blood* / Q000150:complications / Q000401:mortality; D014797:Vital Capacity
chemical_list: D016207:Cytokines; D015850:Interleukin-6