![Anakinra reduces TTP-induced cerebral damage. (A) PS-100b levels at day 3 for the 4 groups of mice: TTP (VWF + placebo, n = 10); TTP + anakinra (VWF + anakinra, n = 10); and 2 control groups (control [vehicle + placebo] and anakinra [vehicle + anakinra], n = 5 for both). One-way ANOVA: P < .001; PS100b levels in TTP: 2975 (2619-3098) pg/mL; controls: 1080 (1075-1085) pg/mL; anakinra 1080 (1070-1080) pg/mL; and TTP + anakinra: 2035 (1558-2018) pg/mL. (B) Change in [18F]FDG brain uptake in mice between day 0 and day 2 for the 4 groups of mice: TTP, n = 5; TTP + anakinra; n = 6; control, n = 6; and anakinra, n = 6. One-way ANOVA: P < .001; Change in [18F]FDG brain uptake in TTP: 1.4 (0.99-1.67) × 10−3 % ID/g; control: 0.25 (0.02-0.69) × 10−3 % ID/g; anakinra: 0.1 (0.0-0.3) × 10−3 % ID/g; and TTP + anakinra: 0.1 (−0.1-0.09) × 10−3 % ID/g. (C) Measurement of [18F]FDG brain PET signal. (D) Change in [99mTc]Tc-DTPA brain uptake between day 2 and day 0 for the 4 groups of mice: TTP, n = 5; TTP + anakinra, n = 6; control, n = 6; and anakinra, n = 6. One-way ANOVA: P < .001. Change in [99mTc]Tc-DTPA brain uptake in TTP: 16.3 (9.89-27.65) × −5 % ID/g; control: 0.72 (0.28-1.51) × 10−5 % ID/g; anakinra: 1.4 (0.6-1.8) × 10−5 % ID/g; and TTP + anakinra: 3.08 (2.06-5.21) × 10−5 % ID/g. (E) Measurement of [99mTc]Tc-DTPA brain SPECT signal. (F) Histological assessment of brain ischemic damage, n = 3 for each group. Percentage of healthy Purkinje cells in TTP: 44%, controls: 65%, anakinra: 70%, and TTP + anakinra: 61%. (G) Brain histology in H&E staining; ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/143/26/10.1182_blood.2023021974/3/blood_bld-2023-021974-gr4.jpeg?Expires=1754060744&Signature=0sIm2vQjDNsaF6MqCSHsIZ3LQM4NBKCg04LbsDxK3WUeJ1wQS7fGB2oX98GZpHZc2Z5EOuE6LGpm8JPJm35-qB0lupzpsnfrwAywYfASivesUvNnb5uRF-c90Wbf-iE4oL3FaNlxZJpIA7J7V3WpP4OSqAFjeJQfQLJ828utYVZDoCKcMWrKJ3MiHMJMJNUWYOvkhEzd2aQAS-CNB1U4DhSQ0Ayx94HotVqRhk60dZtCR3EgN1WLeSEqmqelwaEzd9h6E~4y~AbWJoIcPz61OFtwqzZnUXTfrWr6pt8NuWvkcSi0cPrFjhH4uoNGfr3xfFp0yX1iBvhX9jJJYOLcXg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Anakinra reduces TTP-induced cerebral damage. (A) PS-100b levels at day 3 for the 4 groups of mice: TTP (VWF + placebo, n = 10); TTP + anakinra (VWF + anakinra, n = 10); and 2 control groups (control [vehicle + placebo] and anakinra [vehicle + anakinra], n = 5 for both). One-way ANOVA: P < .001; PS100b levels in TTP: 2975 (2619-3098) pg/mL; controls: 1080 (1075-1085) pg/mL; anakinra 1080 (1070-1080) pg/mL; and TTP + anakinra: 2035 (1558-2018) pg/mL. (B) Change in [18F]FDG brain uptake in mice between day 0 and day 2 for the 4 groups of mice: TTP, n = 5; TTP + anakinra; n = 6; control, n = 6; and anakinra, n = 6. One-way ANOVA: P < .001; Change in [18F]FDG brain uptake in TTP: 1.4 (0.99-1.67) × 10−3 % ID/g; control: 0.25 (0.02-0.69) × 10−3 % ID/g; anakinra: 0.1 (0.0-0.3) × 10−3 % ID/g; and TTP + anakinra: 0.1 (−0.1-0.09) × 10−3 % ID/g. (C) Measurement of [18F]FDG brain PET signal. (D) Change in [99mTc]Tc-DTPA brain uptake between day 2 and day 0 for the 4 groups of mice: TTP, n = 5; TTP + anakinra, n = 6; control, n = 6; and anakinra, n = 6. One-way ANOVA: P < .001. Change in [99mTc]Tc-DTPA brain uptake in TTP: 16.3 (9.89-27.65) × −5 % ID/g; control: 0.72 (0.28-1.51) × 10−5 % ID/g; anakinra: 1.4 (0.6-1.8) × 10−5 % ID/g; and TTP + anakinra: 3.08 (2.06-5.21) × 10−5 % ID/g. (E) Measurement of [99mTc]Tc-DTPA brain SPECT signal. (F) Histological assessment of brain ischemic damage, n = 3 for each group. Percentage of healthy Purkinje cells in TTP: 44%, controls: 65%, anakinra: 70%, and TTP + anakinra: 61%. (G) Brain histology in H&E staining; ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001.
