JAK1 inhibition partially improves survival and disease features in LCMV-induced HLH. (A) Experimental schema for modeling primary HLH, wherein Prf1^−/− mice are infected with LCMV and analyzed day 9 or 30 PI. Probability of survival (B) and clinical scores (C) of naïve, or LCMV- infected Prf1^−/− mice treated with vehicle, itacitinib (120 mg/kg bid), fedratinib (60 mg/kg bid), or ruxolitinib (90 mg/kg bid) from days 4 to 29 PI (5 mice per group). Analysis was performed on day 30 PI. Peripheral blood hemoglobin (D), platelet counts (E), spleen weights (F) shown as percentage of final body weight, and (G-L) serum cytokine levels of mice analyzed on day 9 PI. Data points represent single mice from 5 pooled experiments. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, or ∗∗∗∗P < .0001 by pairwise comparison. For survival, the log-rank test was performed to determine statistical significance between treated groups and vehicle control. For clinical score, statistical significance was determined using two-way ANOVA.