Background Interleukin 6 (IL6) has been associated with modified Rodnan Skin Score (mRSS), interstitial lung disease (ILD), anti-Scl70 and anti-RNA polymerase III antibodies, as well as with ischemic digital ulcers (IDU) and pulmonary hypertension (PH) in patients with Systemic Sclerosis (SSc).
Objectives To evaluate the usefulness of determining plasma IL6 in patients with SS, as a marker of vascular disease. To investigate its association with other clinical manifestations and biological markers of SS.
Methods Patients with Limited SSc (LSSc), Diffuse SSc (DSSc), overlap syndrome and early SSc (ESSc) were consecutively included in this descriptive and cross-sectional study. Serum IL6, biomarkers of disease activity and vascular risk, and autoantibodies were determined. Clinical history was reviewed. Clinical assessment was simultaneously performed, collecting: mRSS, finger flexion and extension, oral aperture measurement, capillaroscopic findings, sHAQ, and Cochin Hand Function Score. Afterward, a vascular surgeon, blinded to clinical findings, underwent ultrasonographic measurement of common carotid intima-media thickness (IMT) and recorded the presence of atheromatous plaques. SPSS Statistics 17.0 was used for data analysis. Spearman coefficient was used to assess the correlation between quantitative variables, and the non-parametric Mann-Whitney and Kruskal-Wallis test were used to compare quantitative and categorical variables. Qualitative variables were compared by means of the X2 statistic.
Results A total of 47 patients were evaluated (29 LSSc, 8 DSSc, 2 ESSc, 8 overlap syndromes): 28% with history of IDU, 9% with PH, 40% with ILD, 12% with heart disease and 30% with gastrointestinal disease (GId). Most of them were female (90%), mean age: 56 years (SD=15), mean disease duration: 11 years (SD=9). The mean mRSS was 8 (SD=8). The mean IMT was 0.6 mm (SD=0.15), 11% of patients having carotid atheromatous plaques. Mean plasma concentrations of IL6 were 4 pg/mL (SD=4). IL6 concentrations showed a positive correlation with pulmonary artery systolic pressure (r=0.583), and were associated with the presence of avascular areas in capillaroscopy (p=0.001). No association was found with previous IDU or the presence of carotid atheromatous plaques, neither with the IMT. Regarding the rest of the variables, IL6 plasma levels showed a positive correlation with CRP (r=0.425), high-sensitivity CRP (r=0.455), fibrinogen (r=0.450), sHAQ (r = 0.449), and disease duration (r=0.434). A negative correlation was found with albumin (r=-0.629). IL6 plasma levels were also associated with GId (p=0.035), joint contractures (p=0.04) and anti Scl70 antibodies (p=0.002). However, IL6 plasma concentrations were lower in patients with anticentromere antibodies (p=0.01).
Conclusions IL6 in SSc patients is a surrogate marker of inflammation and fibrosis, but can also be a marker of microvascular disease. These results should be taken into consideration when planning future clinical trials with IL6 as a therapeutic target for the treatment of this disease.
Disclosure of Interest: None Declared