Figure 3
Figure 3. ST2 blockade reduces morbidity and mortality of FHL2 mice. Prf1−/− mice were infected with LCMV to induce FHL2 and treated with either α-ST2 or control antibodies. (A) Survival of α-ST2-treated mice (n = 9) and control mice (n = 10). Representative of 2 independent experiments. Analyzed by log-rank (Mantel-Cox) test. LCMV-infected WT mice (n = 4) are included for visual comparison. (B) Body weight of α-ST2-treated mice and control mice. Symbols represent mean ± standard error of the mean of 9 to 10 mice. The dagger symbol indicates time points at which control mice died and were excluded from subsequent weight analysis. Representative of 2 independent experiments. Analyzed by linear mixed-effects model to allow for missing data due to mouse mortality: treatment and body weight were modeled as fixed effects, and individual mice were treated as a random effect to account for baseline variability between animals (eg, intercept only). Significance of interaction term (α-ST2 vs control over time) is indicated. LCMV-infected WT mice (n = 4) are included for visual comparison. (C) Body weight of Prf1−/− mice withdrawn from α-ST2 treatment and switched to control antibody at day 18 p.i. or receiving continued α-ST2 treatment. Symbols represent mean ± standard error of the mean of 4 to 5 mice. The † symbol indicates the time point at which 1 withdrawal (w/d) mouse died and was excluded from subsequent weight analysis. Analyzed by linear mixed-effects model as in panel B; significance of interaction term (α-ST2 vs w/d over time) is indicated. Platelet counts (D) and hemoglobin levels (E) in peripheral blood of α-ST2-treated Prf1−/− mice (n = 9) and control Prf1−/− mice (n = 10) 2 days prior to infection and 8 days p.i. Representative of 2 independent experiments. Analyzed by repeated-measures 2-way ANOVA; significance of interaction term (α-ST2 vs control over time) is indicated. Ferritin (F) and soluble CD25 (sCD25) levels (G) in serum 8 days p.i. Data pooled from 2 independent experiments, n = 7 to 8 mice per group. (H-M) Liver pathology in α-ST2-treated Prf1−/− mice (n = 4) and control Prf1−/− mice (n = 4) 8 days p.i. Representative of 2 independent experiments. Analyzed by Student 2-tailed t test. (H) Liver weight, expressed as a ratio of total body weight. (I) Total numbers of intrahepatic leukocytes. (J) Numbers of lobular inflammatory foci per ×20 objective high-power field (hpf), enumerated from hematoxylin and eosin (H&E)-stained tissue sections. Total numbers of intrahepatic CD8+ T cells (K) and CD4+ T cells (L), as measured by flow cytometry. (M) Representative H&E-stained liver sections, original magnification ×200. Severity of microvesicular steatosis was assessed on day 8 p.i. using a standardized scoring system as follows: 0, absent; 1, 1% to 20% of area per ×20 objective hpf; 2, 21% to 40%; 3, 41% to 60%; 4, 61% to 80%; 5, 81% to 100%. *P < .05; **P < .01; ***P < .001.

ST2 blockade reduces morbidity and mortality of FHL2 mice.Prf1−/− mice were infected with LCMV to induce FHL2 and treated with either α-ST2 or control antibodies. (A) Survival of α-ST2-treated mice (n = 9) and control mice (n = 10). Representative of 2 independent experiments. Analyzed by log-rank (Mantel-Cox) test. LCMV-infected WT mice (n = 4) are included for visual comparison. (B) Body weight of α-ST2-treated mice and control mice. Symbols represent mean ± standard error of the mean of 9 to 10 mice. The dagger symbol indicates time points at which control mice died and were excluded from subsequent weight analysis. Representative of 2 independent experiments. Analyzed by linear mixed-effects model to allow for missing data due to mouse mortality: treatment and body weight were modeled as fixed effects, and individual mice were treated as a random effect to account for baseline variability between animals (eg, intercept only). Significance of interaction term (α-ST2 vs control over time) is indicated. LCMV-infected WT mice (n = 4) are included for visual comparison. (C) Body weight of Prf1−/− mice withdrawn from α-ST2 treatment and switched to control antibody at day 18 p.i. or receiving continued α-ST2 treatment. Symbols represent mean ± standard error of the mean of 4 to 5 mice. The † symbol indicates the time point at which 1 withdrawal (w/d) mouse died and was excluded from subsequent weight analysis. Analyzed by linear mixed-effects model as in panel B; significance of interaction term (α-ST2 vs w/d over time) is indicated. Platelet counts (D) and hemoglobin levels (E) in peripheral blood of α-ST2-treated Prf1−/− mice (n = 9) and control Prf1−/− mice (n = 10) 2 days prior to infection and 8 days p.i. Representative of 2 independent experiments. Analyzed by repeated-measures 2-way ANOVA; significance of interaction term (α-ST2 vs control over time) is indicated. Ferritin (F) and soluble CD25 (sCD25) levels (G) in serum 8 days p.i. Data pooled from 2 independent experiments, n = 7 to 8 mice per group. (H-M) Liver pathology in α-ST2-treated Prf1−/− mice (n = 4) and control Prf1−/− mice (n = 4) 8 days p.i. Representative of 2 independent experiments. Analyzed by Student 2-tailed t test. (H) Liver weight, expressed as a ratio of total body weight. (I) Total numbers of intrahepatic leukocytes. (J) Numbers of lobular inflammatory foci per ×20 objective high-power field (hpf), enumerated from hematoxylin and eosin (H&E)-stained tissue sections. Total numbers of intrahepatic CD8+ T cells (K) and CD4+ T cells (L), as measured by flow cytometry. (M) Representative H&E-stained liver sections, original magnification ×200. Severity of microvesicular steatosis was assessed on day 8 p.i. using a standardized scoring system as follows: 0, absent; 1, 1% to 20% of area per ×20 objective hpf; 2, 21% to 40%; 3, 41% to 60%; 4, 61% to 80%; 5, 81% to 100%. *P < .05; **P < .01; ***P < .001.

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