Fig 5.

Late intervention in the sHLH continues to afford clinical benefit. Mice (n = 8 per time point) were injected with 50 μg of CpG-ODN at days 0, 2, 4, and 7 (gray filled triangles) and administered 100 mg/kg of the anti-IFNγ mAb, XMG1.2 (dotted line), or an isotype control mAb (solid line), on days 4 and 6 (black filled triangles). (A) IL-6 and TNFα serum concentrations were quantified in a multiplex assay using the Luminex technology; body and spleen weights were monitored and blood parameters including lymphocyte, platelet and red blood cell counts were measured using a hemavet analyzer and serum ferritin was measured by ELISA. (B) Liver inflammation was evaluated on day 8 by calculating the area that contained foci of leukocyte infiltration as illustrated in (B). The graph represents the quantitative analysis of at least 9 fields per liver capturing the fold increase of area as compared to untreated mice (ie, no CpG injection); each symbol represents an individual mouse; horizontal lines represent the mean values. IL-6 and TNFα mRNA levels were evaluated by qPCR in the liver. The samples from day 0 were collected before the CpG-ODN injection, whereas samples from day 4 and day 7 were collected 6 hours after CpG-ODN injection. Samples from the day of a mAb administration were collected before the injection. Values are the mean ± standard error of the mean. Data are representative of 1 experiment. Statistics were performed at each time point between isotype control and XMG1.2-treated groups. ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001 were obtained using the 1-tailed nonparametric Mann–Whitney U t test. AU, arbitrary unit; IL-6, interleukin 6; TNFα, tumor necrosis factor α; mRNA, messenger RNA; qPCR, quantitative PCR; sHLH, secondary hemophagocytic lymphohistiocytosis.