JAK1 inhibition improves survival and clinical scores in CpG/αIL-10R-induced HLH. (A) Experimental schema for modeling secondary HLH, wherein WT C57BL/6J mice receive injections of CpG and αIL-10R antibody on days 0, 2, 4, and 7, and are then analyzed on day 9 or 10 after the first injection. (B) Probability of survival (B) and clinical scores (C) from naïve, or CpG/αIL-10R-treated mice who received vehicle, itacitinib (120 mg/kg twice daily [bid]), fedratinib (60 mg/kg bid), or ruxolitinib (90 mg/kg bid) from days 4 to 9 after first CpG/αIL-10R injection. Analysis was performed on day 10. Data are combined from 2 independent experiments (9-10 mice per group). (D) Spleen weights shown as percentage of final body weight in mice treated with vehicle, itacitinib (120 mg/kg bid), fedratinib (60 mg/kg bid), or ruxolitinib (90 mg/kg bid) on days 4 to 8 after the first CpG/αIL-10R injection. Analysis was performed on day 9. Peripheral blood hemoglobin (E), hematocrit (F), and platelet counts (G). Data points in panels D-G represent single mice from 3 pooled experiments. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, or ∗∗∗∗P < .0001 by pairwise comparison. For survival, log-rank test was performed to determine significance between treated groups and vehicle control. For clinical score, statistical significance was determined using two-way ANOVA.