EFFECTS OF INTERLEUKIN-18 ANTIBODY ON IMMUNE LIVER INJURY IN MICE

PING WANG1^, YING-JIAN ZHANG², YI-RAN LI², XIAO-YAN XIA¹, SHU-YAN LV¹

¹Department of Preventice Medicine, Henan University of Science and Technology, Luoyang 471023, China - ²Department of Gastroenterology, First Affiliated Hospital Henan University of Science and Technology, Luoyang 471003, China

Introduction: Anti-IL18 antibody was applied to inhibit IL-18, regulate the cytokine network, inhibit liver immune injury, and exert a protective effect against immune liver injury. The present study aimed to explore the immunological mechanism of the effect of anti-IL18 antibody on immune liver injury in mice, and appropriate dose of antibody intervention, in order to provide theoretical and animal experimental evidence for the treatment of immune liver injury.

Materials and methods: Bacillus Calmette-Guérin (BCG) and lipopolysaccharide (LPS) were used to establish an animal model of immune liver injury. For the intervention group, the high and low doses of anti-IL18 antibody were intraperitoneally injected on day 2, 7 and 12. The control and model groups were intraperitoneally administered with normal saline. From the following day, the positive control group was intragastrically administered with bifendate pills, daily. Serum levels of alanine transaminase (ALT), aspartate tran- saminase (AST), IL-18, interleukin-1 (IL-1), and tumor necrosis factor alpha (TNF-α) were measured after 12 days. The liver, spleen and thymus gland were removed, and the weight coefficients were calculated. Liver tissue was collected and sectioned for hematoxylin- esosin staining (H&E) and Van Gieson’s staining.

Results: The results revealed that the coefficients of the injured liver, spleen and thymus in the high-dose antibody intervention group were significantly decreased compared with those in the model group (P<0.05). Furthermore, ALT and AST levels were all signifi- cantly lower in the high-dose, low-dose and positive control groups, compared with the model group (P<0.01). The high-dose interven- tion group exhibited a significantly inhibited increase in IL-18, IL-1 and TNF-α (P<0.05). Furthermore, in the high- and low-dose anti- body intervention groups, and positive control group, the pathological liver damage was reduced to varying degrees, while the cytologi- cal grades of liver cell injury were significantly different among these groups (X2 = 14.667, P<0.01).

Discussion and conclusions: These results indicate that immune liver injury in antibody intervention mice could be alleviated, and this was most significant in the high-dose group. High- and low-dose antibody intervention inhibited the immune injury of the liver, thereby playing a protective role in mouse immune liver injury.