Fig. 4.

GM-CSF neutralisation inhibits intrahepatic CD206⁺macrophage accumulation and fibrosis in viral-induced liver disease.

(A) Schedule of anti-GM-CSF antibody treatment in HBV-infected humanised mice wpi. (B) Serum sCD14 concentrations (ng/ml) in HBV-infected humanised mice untreated (n = 9) and treated with anti-GM-CSF antibody (prophylactic group, n = 8-9) followed longitudinally. (C) Measurement of human serum ALT in control (Ctrl, n = 7), prophylactic (n = 6) and therapeutic (n = 6) groups of HIL mice at 0, 6 and 10 wpi. p values comparing mice from the same groups or comparing groups of mice at 10 wpi were obtained using the paired Wilcoxon and the Mann-Whitney non-parametric tests, respectively. (D) Density of intrahepatic CD14⁺HLA-DR^hiCD206⁺ macrophages in HBV-infected mice at 10 wpi that were untreated (n = 9) or that received anti-GM-CSF antagonistic antibody at 0 wpi (prophylactic group, n = 8) or at 6 wpi (therapeutic group, n = 7) expressed as number of cells per gram of liver tissue. (E) H&E (upper panels) and Sirius Red (lower panels) staining of the liver of representative humanised mice from the 3 groups are shown. (F) % fibrosis quantification in all animals in the 3 groups. (G) Expression of human pro-fibrotic genes within HIL mouse livers at 10 wpi relative to the hALB (human albumin) gene. (H) Correlation of the % liver fibrosis with numbers of intrahepatic CD206⁺ macrophages (black, Ctrl; blue, prophylactic; red, therapeutic). p values calculated by Mann-Whitney test for (B,D,F), and by Spearman's correlation for (B). ALT, alanine aminotransferase; wpi, weeks post infection.