Endothelial Activation in Mild Scorpion Envenoming: Role of Interleukin-6

Scorpion envenoming is primarily recognized as a neurotoxic syndrome, but increasing evidence suggests that inflammatory responses may contribute to its systemic effects. The clinical relevance of these responses in patients with mild envenoming remains poorly characterized. This study investigated serum interleukin-6 (IL-6) and its association with angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in adults with mild Tityus stigmurus envenoming. A cross-sectional study was conducted in 80 adults treated for scorpion envenoming at a referral hospital in Northeast Brazil, between August 2025 and April 2026. Clinical, hematological, biochemical, and serum biomarker parameters were evaluated. IL-6, Ang-1, and Ang-2 were quantified by enzyme-linked immunosorbent assay. Patients were classified according to detectable or undetectable serum IL-6, using 7 pg/mL as the assay detection threshold. All patients had mild envenoming, no systemic clinical manifestations, and favorable outcomes. IL-6 was detectable in 17 patients (21.3%). Patients with detectable IL-6 had higher Ang-2 concentrations than those with undetectable IL-6 (3.94 vs. 1.03 ng/mL, p = 0.006) and a higher Ang-2/Ang-1 ratio (0.091 vs. 0.027, p = 0.003). Ang-1 concentrations did not differ between groups (p = 0.524). IL-6 showed a moderate positive correlation with Ang-2 (ρ = 0.549, p = 0.022). Conventional hematological, renal, hepatic, and pancreatic parameters did not differ significantly according to IL-6 status. These findings indicate that mild T. stigmurus envenoming may induce detectable inflammatory activation despite the absence of systemic clinical manifestations. The association between IL-6 and Ang-2 suggests a link between inflammatory and endothelial responses and supports IL-6 as a candidate marker for investigating the clinical effects of scorpion venom.