Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice

Figure 1 Interleukin (IL)-1β, interleukin 1 receptor antagonist (IL-1Ra) and IL-6 expression after carbon tetrachloride (CCl₄) (1 mL/kg) administration. A: Quantification of IL-1β mRNA levels; B: IL-1Ra mRNA levels; C: Serum IL-1β; D: Serum IL-1Ra; E: Ratio of serum level of IL-1Ra to IL-1β; F: Quantification of IL-6 mRNA levels of the livers treated with recombinant human IL-1Ra (rhIL-1Ra) or PBS. ^aP < 0.05, ^bP < 0.01.

Figure 2 Acute liver injury (1 mL/kg CCl₄ administration) ± rhIL-1Ra. A: Serum aspartate aminotransferase (AST); B: Serum alanine amino transferase (ALT), with rhIL-1Ra or PBS; C: Necrotic areas. Representative findings from at least 12 mm² tissue sections were counted for each mouse; D-F: Hematoxylin and eosin (HE) stained liver sections; D: Group received PBS at day 3 after CCl₄ administration, shows necrosis with clusters of inflammatory cells around central vein (original magnification, × 100); E: Group received rhIL-1Ra at day 3 after CCl₄ administration, demonstrates mostly histological recovery with only inconspicuous necrosis still remaining around central vein and very few inflammatory cells are present (original magnification, × 100); F: Normal liver histology with rhIL-1Ra treatment, which shows no difference from normal liver tissue histology. ^aP < 0.05, ^bP < 0.01.

Figure 3 Immunostaining of proliferating cell nuclear antigen (PCNA) shows rhIL-1Ra promotes hepatocyte proliferation. A: Normal liver (original magnification, × 100); B: Normal liver in rhIL-1Ra treated mice (original magnification, × 100); C: Group received rhIL-1Ra at day 2 after CCl₄ administration, numerous PCNA⁺ hepatocytes in centrilobular areas and scattered PCNA⁺ hepatocytes at the edge of hepatocellular necrosis (original magnification, × 200); D: Group received PBS at day 2 after CCl₄ administration, few PCNA⁺ hepatocytes in centrilobular areas at day 2 (original magnification, × 200); E: Group received rhIL-1Ra at day 3 after CCl₄ administration, numerous positive cells in centrilobular areas around central vein (original magnification, × 100); F: Group received PBS at day 3 after CCl₄ administration shows fewer numbers of positive cells (original magnification, × 100); G: Numbers of PCNA⁺ cells after CCl₄ administration with rhIL-1Ra or PBS, at least 12 mm² tissue sections were counted for each mouse. Arrows point to PCNA+ hepatocytes. ^bP < 0.01.

Figure 4 rhIL-lRa treatment increased probability of survival after a lethal dose administration of CCl₄ (2. 6 mL/kg). Mice were administered with either PBS as a control (n = 20) or rhIL-1Ra (n = 20) twice a day for 5 d. Survivals were scored twice a day for 5 d, and the results were analyzed using the log-rank test and expressed as the Kaplan-Meier survival curves. P = 0.006.