Ruxolitinib (Ruxo) targets inflammation in a murine model of secondary HLH via IFN-γ–dependent and -independent mechanisms. (A) WT C57BL/6 mice were injected with PBS (Naive) or with CpG and αIL-10R, as shown. Injected mice were left untreated (UnRx) or were treated with αIFN-γ or Ruxo on days 4 to 8 after the first CpG and αIL-10R injection. On day 9, mice were euthanized and analyzed. (B) Change in body weight (as a percentage of the initial body weight) during the course of the experiment. Body weight percentage was calculated as (actual body weight/initial body weight) × 100. Peripheral blood samples were analyzed for the number of platelets (PLT) (C) and the numbers red blood cells and for the levels of hemoglobin (Hb) (D). (E) Levels of serum cytokines were determined using Luminex. (F) Splenomegaly was assessed as a percentage of body weight and calculated as (spleen weight/actual body weight) × 100. (G) Hepatomegaly was assessed as a percentage of body weight and was calculated as: (liver weight/actual body weight) × 100. Each data point represents 1 mouse, and data were collected from 3 independent experiments. Outliers were excluded using Grubb’s test. Data shown are the mean values ± standard deviation. The total number of mice per group was n = 12 each (Naive and UnRx), n = 14 (αIFN-γ), and n = 13 (Ruxo). *P < .05, **P < .01, ***P < .001, ****P < .0001.