AB0630 Expression of tnf-Α and il-6 in systemic lupus erythematosus: relationship with disease activity
Authors: T.A. Panafidina, T.V. Popkova, A.A. Novikov, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Cytokines play an important role in the pathogenesis of SLE. TNF-a, IL-6 are the cytokines with suggested proinflammatory and immunoregulatory actions in the pathogenesis of SLE with differential effects on B or T cells, as well as on programmed cell death. Fas/APO-1 and Fas ligand (FasL) are involved in the apoptosis. FasL is a marker of apoptosis, it induces cell apoptosis when binds to Fas/APO-1. Both are expressed in membrane-associated and soluble forms (sFas/APO-1 and sFasL). sFas/APO-1 is known to inhibit the apoptosis via blocking the binding of Fas/APO-1 to FasL/sFasL. <h3>Objectives</h3> We evaluated the levels of IL-6 and TNF-α and their possible association with disease activity, apoptosis markers. <h3>Methods</h3> The study included 52pts (89% female, age 30,0 [26,5–44,5 years] (median [interquartile range 25% &gt;75%])) with SLE ACR, 1997 and 20 controls (100% female without any rheumatic and infectious diseases, age 30,0 [25,0–39,5 years]). SLE-related factors, including disease duration, clinical features, SLE Disease Activity Index (SLEDAI 2K) and Systemic Lupus International Collaborating Clinics (SLICC) damage index were evaluated in parallel with relevant laboratory findings, autoantibodies. Serum levels of IL-6 and TNF-α (pg/ml), sFas/APO-1 (pg/ml) and sFasL (ng/ml) were measured by ELISA (Bender MedSystem GmbH, Austria). <h3>Results</h3> Median SLE duration was 5 [1–11] years, SLEDAI 2K–9,5 [4,0–16,0], SLICC-0 [0–1], current prednisone dose–5,0 [0–11,9] mg/day, 44% of pts received hydroxychloroquine, 17% &gt;cyclophosphamide, 10% &gt;azathioprine, 4% &gt;mycophenolate mofetil, 8% &gt;biologics. SLEpts had higher level of IL-6 vs control(2,9 [1,5–9,7] vs 1,4 [0,7–2,1] pg/ml, p<i>&lt;0,01</i>) and lower level of TNF-α(1,9 [0,5–3,2] vs 4,5 [3,5–6,4] pg/ml, p<i>&lt;0,0001</i>), lower levels of sFas/APO-1 vs control (657,5 [483,2–791,4] vs 1456,9 [426,5–2060,8] pg/ml, p&gt;<i>0,05</i>) and lower levels of sFasL vs control (0,01 [0,01–0,03] vs 0,07 [0,05–0,10] ng/ml, p&lt;<i>0,0001</i>). In SLE pts serum level IL-6 correlated with IgM (r=0,69, p<i>&lt;0,01</i>), K<sup>+</sup>(r=0,43, p<i>&lt;0,01</i>), TNF-α(r=0,50, p<i>&lt;0,001</i>), APRIL(r=0,39, p<i>&lt;0,01</i>) and sFas/APO-1 levels(r=0,29,p<i>&lt;0,05</i>); TNF-α level correlated with SLICC(r=0,32, p&lt;0,05), APRIL (r=0,42, p&lt;0,01), IL-6(r=0,50, p<i>&lt;0,001</i>), haemoglobin concentration(r=0,39,p<i>&lt;0,01</i>), sFasL (r=0,44, p&lt;0,01) and total cyclophosphamide dose (r=0,28,p<i>&lt;0,05</i>). We divided SLEpts on two groups: the 1st-pts (n=31) with high activity (SLEDAI 2K≥8), the 2nd–pts (n=21) with low (SLEDAI 2K&lt;8). The pts in the 1st group had lower level of TNF-α compared to 2nd(1,6 [0,3–2,2] vs 2,8 [1,3–4,5] pg/ml, p<i>&lt;0,05</i>), with no difference in IL-6 level. <h3>Conclusions</h3> SLEpts demonstrated higher IL-6 and lower TNF-α levels as compared to healthy controls. Pts with high activity of SLE had decreased level of TNF-α. There is no correlation between disease activity and IL-6 level, as well as between elevated IL-6 and acute phase indicators. We suggest an immunoregulatory not proinflammatory role of IL-6 in SLE and probable protective role of TNF-α in SLE pathogenesis (it's deficiency can lead to the development and high activity of SLE). There was no correlation between IL-6, TNF-α levels and any SLE features. The correlation of IL-6 with sFas/APO-1 level (apoptosis inhibitor that blocks binding of sFas/APO-1 to sFasL) and TNF-α with sFasL concentration (a marker of apoptosis) suggests their different roles in the mechanisms of apoptosis. <h3>Disclosure of Interest</h3> None declared