Elevated Interleukin-6 Levels in Socioeconomically Disadvantaged Children With Borderline Subclinical Rheumatic Heart Disease in São Paulo, Brazil: A Prospective Cohort Study Highlighting Early Detection and Treatment Opportunities.
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BACKGROUND: Subclinical rheumatic heart disease (SCRHD) is the precursor to symptomatic disease, yet the cytokine profile of its earliest borderline stage remains uncharacterized. It is unknown whether inflammatory markers persist longitudinally in subclinical rheumatic heart disease. This study characterized the cytokine profile in borderline SCRHD at baseline and evaluated its longitudinal evolution over a 2-year period in the combined SCRHD (borderline and definitive). METHODS: In a prospective cohort study, 1026 children (5-15 years) from disadvantaged areas of São Paulo, Brazil, underwent echocardiographic screening. Participants were classified as normal, borderline SCRHD, or definite SCRHD according to World Health Organization criteria. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor-alpha, and other cytokines were measured at baseline (T0) and after 2 years (T1). RESULTS: The prevalence of SCRHD was 7.6% (95% CI, 6.0%-9.2%), with 6.7% borderline (95% CI, 5.2%-8.2%) and 0.9% as definite (95% CI, 0.3%-1.5%). At baseline, IL-6 levels were significantly higher in the borderline SCRHD group compared with controls (P=0.048), while tumor necrosis factor-alpha showed a trend toward elevation (P=0.067). No significant differences were observed for interleukin-2 (P=0.067), interleukin-4 (P=1.000), interleukin-10 (P=0.690), interleukin-17A (P=0.067), or interferon-gamma (P=0.456). Among 44 participants followed for 2 years, IL-6 and tumor necrosis factor-alpha levels remained persistently elevated, with no significant change over time (P=0.626 and P=0.144, respectively), indicating ongoing inflammatory activity. CONCLUSIONS: Borderline SCRHD is marked by elevated IL-6 levels that last for at least 2 years, indicating a sustained proinflammatory state from the earliest detectable stage of the disease. These findings identify interleukin-6 as a potential early biomarker and therapeutic target to prevent the progression of SCRHD.