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Background: Lupus myocarditis (LM) is a serious manifestation of systemic lupus erythematosus (SLE) that occurs in 5-10 % of patients. Cardiac MRI (CMR) is the non-invasive diagnostic modality of choice, characterizing myocardial tissue injury [1]. Acute myocardial oedema/ inflammation is reflected by an increased T2 -weighted signal. An increased T1 signal represents inflammation as well as necrosis/fibrosis if accompanied by late gadolinium enhancement (LGE) [1]. LM is typically non-uniform, affecting different segments of the myocardium in a non-ischemic distribution. Serum cytokines (interleukin [IL]-18, IL-17, IL-1Ra and vascular cell adhesion molecule [sVCAM], but not IL-6) correlate with myocardial injury detected on CMR in SLE patients [2]. IL-6 is a pleiotropic cytokine with diverse signaling functions. In contrast to its pro-inflammatory signaling, short-term elevation of IL-6 is protective in ischemic and viral mediated myocardial injury [3, 4]. The role of IL-6 in the immunopathogenesis of LM has not been explored.
Objectives: To assess the relationship of serum (sIL-6) and tissue IL-6 (tIL-6) levels with imaging indicators of myocardial dysfunction and injury in patients with LM.
Methods: A cross-sectional study including 14 SLE patients with symptomatic LM and 13 non-LM SLE control patients was performed between May 2022 and March 2024. A LM diagnosis was based on clinical, echocardiographic and CMR findings. Serum cytokine profiles were determined by ELISA and compared between the two groups. LM patients underwent an endomyocardial biopsy (EMB), including histopathology assessment and tissue cytokine analyses using immunohistochemistry and quantitative fluorescent imaging.
Results: All patients were female and fulfilled the 2019 EULAR/ACR classification criteria. LM patients had a mean±SD age of 30.4±9.2 years, high SLE disease activity index (SLEDAI-2K:12.8±5.9) and recent diagnosis of SLE (median 7 weeks). SLE controls were 32±9.7 years old with a median SLEDAI-2K of 8 (IQR:4-15). Serum TNF-alpha (r=0.535; p=0.005) and sVCAM (r=0.622; p<0.001) but not sIL-6 levels correlated with SLE disease activity (n=27). Serum IL-10 and sVCAM levels were higher in LM than SLE control patients (p=0.044 and p=0.04), with no significant differences in sIL-6 levels. EMB was done in all 14 LM patients. A lymphocytic infiltrate was observed in 3/14 patients, yet no patient fulfilled the Dallas Criteria for myocarditis [5]. No correlation was observed between serum and tissue levels of IL-6 (r= -0.231; p=0.471). sIL-6 negatively correlated with tissue bone morphogenetic protein-7 (tBMP-7 r= -0.571; p=0.041). This was not true for tIL-6 and tBMP-7. 2D-echocardiography was used to assess global and regional left ventricular (LV) function. The mean LV ejection fraction (LVEF) in the LM patients was 44% (±9.2) and the mean regional wall motion score index (WMSi) was 1.45 (±0.16; normal≤1). CMR was performed in 13/14 LM patients: 10 fulfilled the Lake Louise Criteria for myocarditis with increased T2-weighted signaling in 6/13, increased T1-signaling in 11/13 and LGE in 7/13 patients [1]. In LM patients, echocardiographic analyses demonstrated a positive correlation between sIL-6 and the WMSi (r=0.678; p=0.015), representing regional LV dysfunction. Evidence of myocardial injury on CMR positively correlated with creatinine kinase (r=0.61; p=0.081) and high sensitivity troponin-T (r=0.67; p=0.024) levels. This was particularly evident for the T1-signals in 7/10 mid- and apical segments of the LV. sIL-6 showed a positive correlation with the T2-signal in the apical segments (r=0.659; p=0.038), but no correlation with T1-signals on CMR. In contrast, tIL-6 negatively correlated with T1 and T2-signals (r= -0.478; p=0.098 and r= -0.517; p=0.07). These correlations were most significant in the basal and middle segments (e.g. T1: Anterior basal septum, r= -0.818; p=0.001 and T2: Mid-inferior septum, r= -0.720; p=0.019. tBMP-7, a potentially protective signalling role player, negatively correlated with predominantly mid and apical T2-signals (e.g. mid-posterior segment: r= -0.815; p=0.002) [6].
Conclusion: Serum IL-6 levels were increased in both LM and SLE control patients. Levels were not significantly different between the two groups and did not correlate with SLE disease activity. No correlation was observed between serum and endomyocardial tissue IL-6 levels in patients with LM, suggesting different immunopathogenetic contexts. Higher tIL-6 levels correlated with a lesser degree of myocardial oedema, inflammation and necrosis, based on T1 and T2-signals on CMR, in particular in the mid- and basal LV segments. These findings at endomyocardial tissue level suggest a possible protective effect of increased endomyocardial tissue IL-6 expression at the presentation of LM, limiting the degree of myocardial injury.
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Acknowledgements: NIL.
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (