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Evaluation of Dose-Dependent Efficacy and Mechanisms of Aspirin Combined with Intravenous Immunoglobulin in a Murine Model of Kawasaki Disease Vasculitis

Year: 2026

Type: article

Abstract: The requirement and molecular contribution of acute high-dose aspirin (ASA) in the treatment of Kawasaki disease (KD) remain clinically controversial. This study aimed to investigate the dose-dependent mechanism and pharmacodynamics of adjunctive ASA in an experimental KD mouse model. Male C57BL/6 mice were injected with Lactobacillus casei cell wall extract (LCWE; 100 µg/day, Days 1–7) to induce systemic coronary arteritis. On Day 14, mice received intravenous immunoglobulin (IVIG) (2 g/kg, i.p.) monotherapy (G3) or IVIG combined with High-dose (100 mg/kg; G4), Medium-dose (50 mg/kg; G5), or Low-dose ASA (5 mg/kg; G6) daily via oral gavage for 3 days (Days 14–16), followed by a 5-day drug washout until sacrifice on Day 21. Coronary vasculitis and internal elastic lamina integrity were quantified using H&E and Verhoeff–Van Gieson (VVG) staining. Heart tissue activation of p-nuclear factor kappa-B (NF-κB) and downstream matrix metalloproteinance-9 (MMP-9) expression were evaluated by Western blot. High-dose ASA combined with IVIG (G4) achieved statistically superior suppression of upstream NF-κB phosphorylation (p-NF-κB/NF-κB ratio) and perivascular leukocyte infiltration compared to IVIG monotherapy (G3) (p < 0.05). This acute upstream blockade directly preserved arterial wall architecture, with G4 demonstrating near-baseline structural restoration of the internal elastic lamina on VVG scoring (G4 vs. G3, p < 0.05). Following the 5-day drug washout, downstream MMP-9 expression in G4 converged with G3 levels due to pharmacodynamic waning, whereas suboptimal mid/low-dose ASA regimens (G5/G6) displayed lingering MMP-9 elevation, indicating persistent low-grade matrix remodeling. Acute high-dose ASA provides a non-redundant, synergistic anti-inflammatory effect alongside IVIG to prevent early elastolysis. Maintaining adequate acute ASA dose followed by careful post-withdrawal tapering is vital to prevent delayed arterial wall remodeling and coronary aneurysm progression.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27219783