IL-18BP reduces fibrosis and improves function in SCD hearts. (A-B) Representative pictures of Masson trichrome staining with vehicle vs IL-18BP-exposed hearts in SCD mice. (C-E) Fibrosis area percentage was significantly higher in SCD mice LV and RV tissues compared with CTR heart tissues (C) and was reduced in SCD mice with exposure to IL-18BP (total myocardium: CTR + vehicle, 2.08% ± 0.25% [n = 6]; CTR + IL-18BP, 1.80% ± 0.18% [n = 6]; SCD + vehicle, 6.25% ± 0.29% [n = 7]; SCD + IL-18BP, 4.27% ± 0.29% [n = 7]; ANOVA P < .01). (C) IL-18BP significantly reduced fibrosis levels in both the LV and the RV (ANOVA P < .01) as well as (D) in both perivascular and interstitial myocardium (ANOVA P < .01) and (E) perivascular myocardium (ANOVA P < .01) in SCD mice. ANOVA and post hoc *P < .05, **P < .01. (F) Diastolic function was improved (reduced delta E/e′ or smaller E/e′ after IL-18BP treatment) with exposure to IL-18BP in SCD mice (ANOVA P = .04) (n = 4 for vehicle and n = 9 for IL-18BP group). (G) SCD mice exposed to IL-18BP for 4 weeks manifested a reduced change in LV end diastolic volume (eg, smaller volumes) vs vehicle (n = 4 for vehicle; n = 9 for IL-18BP group). (H-I) Chronic IL-18 inhibition is associated with reduced activated NF-κB protein levels in SCD mouse hearts. Phosphorylated NF-κB (p-NF-κB) is higher in SCD hearts (*P < .05) compared to CTR group and inhibited (**P < .01) in SCD with IL-18BP injection (n = 5 mice per group). Median values displayed with whiskers using the Tukey method.