PRMT5 inhibition reduces pathology in a murine model of secondary HLH. (A) Schema of mouse studies. HLH was induced with CPG-1826 and anti–IL-10R on days 0, 2, 4, and 7. PRT382 was dosed daily starting on day 0 (9 days of treatment [TX]), 2 (7 days of TX), or 4 (5 days of TX). Ruxolitinib (Rux) was given twice daily from day 4 to 8. Mice were sacrificed on day 9 and samples were processed for additional analysis. (B) Average weight of each cohort as a percentage change from day 0 in healthy mice, induced HLH with no TX, induced HLH with Rux TX, or HLH with PRT382 TX started on day 0, 2, or 4. Average spleen (C) and liver (D) mass as a percentage of mouse body weight in each cohort determined on necropsy. (E) RBC count, (F) hemoglobin concentration, and (G) lymphocyte count from complete blood counts on blood on day 9. Error bars show standard deviation. A Kruskal-Wallis test with Dunn test for multiple comparisons was used in panel B and 1-way analysis of variances (ANOVAs) with Tukey multiple comparisons were used in panels C-G to determine significance. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. RBC, red blood cell.