title: The mechanism of how anti-IL-18 prevents concanavalin-A-induced hepatic fibrosis on a mouse model.
abstract: BACKGROUND
  The administration of concanavalin A (ConA) induces severe hepatic fibrosis in mice. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) were the key cytokines involved in the process. The aim of this research was to explore the effects and the mechanisms of IL-18 and anti-IL-18 on hepatic fibrosis in a ConA induced hepatic fibrosis model in BABL-C mice.
  
  
  METHODS
  One hundred eighty BABL-C mice were randomly divided into five groups (Group a, b, c, d, e). The mice were administered saline, immunoglobulin G, ConA, IL-18 + ConA, Anti-IL-18 + ConA, respectively. At 1, 7, 14, 21 wk, the levels of serum alanine aminotransferase, TNF-alpha, IFN-gamma, IL-4, matrix metalloproteinase (MMP)-2-RNA, and tissue inhibitor of metalloproteinase-1-mRNA were measured.
  
  
  RESULTS
  The levels of serum TNF-alpha and IFN-gamma detected in the IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). Similarly, the levels of MMP-2-RNA and tissue inhibitor of metalloproteinase-1-mRNA expressed in IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). A majority of these cytokines was secreted by CD4(+)T cells.
  
  
  CONCLUSIONS
  The immunological response to hepatic fibrosis by repeated injection of ConA in the mouse model was aggravated by IL-18 and blocked by anti-IL-18.
authors.affiliation: The Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Li
authors.forename: Xinli
authors.initials: X
authors.lastname: Huang
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Meng
authors.forename: Wan Y
authors.initials: WY
authors.lastname: Lau
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology* / Q000494:pharmacology*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000906:Antibodies; D020382:Interleukin-18; D008934:Mitogens; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma; D020778:Matrix Metalloproteinase 2