Figure 5
Figure 5. Hepatic toxicity associated with αCD40 monotherapy is reversed with TLR7 agonism. (A,B) Kinetic analysis of serum transaminases. Mice were treated with PBS, 100 μg αCD40, 100 μg TLR7*, or both intravenously. Serum was isolated at various time points afterward, and serum levels of alanine transaminase (A) or aspartate transaminase (B) were measured as described. Data are representative of 3 independent experiments, with n = 3 to 8 mice per group, per time point. (C-F) Histologic analysis of livers treated with PBS (C), 100 μg αCD40 (D), 100 μg TLR7* (E), or 100 μg αCD40 and 100 μg TLR7* (F) for 48 hours. (G) Semiquantitative assessment of histopathologic changes in livers from mice treated as above for 48 hours. Data are pooled from 2 independent experiments, with n = 6 mice in each treatment group. P = .026 by Mann-Whitney nonparametric test.

Hepatic toxicity associated with αCD40 monotherapy is reversed with TLR7 agonism. (A,B) Kinetic analysis of serum transaminases. Mice were treated with PBS, 100 μg αCD40, 100 μg TLR7*, or both intravenously. Serum was isolated at various time points afterward, and serum levels of alanine transaminase (A) or aspartate transaminase (B) were measured as described. Data are representative of 3 independent experiments, with n = 3 to 8 mice per group, per time point. (C-F) Histologic analysis of livers treated with PBS (C), 100 μg αCD40 (D), 100 μg TLR7* (E), or 100 μg αCD40 and 100 μg TLR7* (F) for 48 hours. (G) Semiquantitative assessment of histopathologic changes in livers from mice treated as above for 48 hours. Data are pooled from 2 independent experiments, with n = 6 mice in each treatment group. P = .026 by Mann-Whitney nonparametric test.

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