AUTHOR=Schubert Christian , Seizer Lennart , Chamson Emil , König Paul , Sepp Norbert , Ocaña-Peinado Francisco M. , Schnapka-Köpf Mirjam , Fuchs Dietmar 

TITLE=Real-Life Cause-Effect Relations Between Urinary IL-6 Levels and Specific and Nonspecific Symptoms in a Patient With Mild SLE Disease Activity

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.718838

DOI=10.3389/fimmu.2021.718838

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Little is known about the real-time cause-effect relations between IL-6 concentrations and SLE symptoms.</p></sec><sec><title>Methods</title><p>A 52-year-old woman with mild SLE activity collected her entire urine for the determination of IL-6/creatinine and protein/creatinine levels (ELISA, HPLC) for a period of 56 days in 12 h intervals (total: 112 measurements). Additionally, she answered questionnaires (VAS) on oral ulceration, facial rash, joint pain, fatigue and tiredness and measured her temperature orally twice a day. Time-series analyses consisted of ARIMA modeling and cross-correlational analyses (one lag = 12 h, significance level = <italic>p</italic> &lt; 0.05).</p></sec><sec><title>Results</title><p>Statistical analyses showed that increased urinary IL-6 concentrations preceded increased urinary protein levels by 36–48 h (lag3: r=+.225; <italic>p</italic>=.017) and that, in the opposite direction of effect, increased urinary protein preceded urinary IL-6 decreases by 12–24 h (lag1: r=–.322; <italic>p</italic>&lt;.001). Moreover, urinary IL-6 increases co-occurred with increased oral ulceration (lag0: r=+.186; <italic>p</italic>=.049); after 48–60 h, however, IL-6 increases showed a strong tendency to precede oral ulceration decreases (lag4: r=–.170; <italic>p</italic>=.072). Increases in facial rash preceded decreases in urinary IL-6 after 84–96 h (lag7: r=–.215; <italic>p</italic>=.023). As to fatigue, increases in urinary IL-6 co-occurred with decreased fatigue (lag0: r=–.193; <italic>p</italic>=.042); after 84–96 h, however, IL-6 increases preceded fatigue increases (+lag7: <italic>r</italic>=+.189; <italic>p</italic>=.046). Finally, joint pain, tiredness and body temperature did not significantly correlate with urinary IL-6 concentrations in either direction of effect.</p></sec><sec><title>Conclusions</title><p>The results of this evaluation point to real-life feedback mechanisms between immune activity and SLE symptoms. Comparison with a previous evaluation of this patient suggests a counterregulatory mechanism between Th1 activity and IL-6. These findings are preliminary and require replication to draw firm conclusions about the real-time relation between IL-6 and SLE disease activity.</p></sec>