PMID- 17559879 OWN - NLM STAT- MEDLINE DCOM- 20071002 LR - 20081121 IS - 0022-4804 (Print) IS - 0022-4804 (Linking) VI - 142 IP - 1 DP - 2007 Sep TI - The mechanism of how anti-IL-18 prevents concanavalin-A-induced hepatic fibrosis on a mouse model. PG - 175-83 AB - 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. MATERIALS AND 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. FAU - Zhang, Yewei AU - Zhang Y AD - The Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, China. FAU - Li, Ping AU - Li P FAU - Li, Guoqiang AU - Li G FAU - Huang, Xinli AU - Huang X FAU - Meng, Qingyang AU - Meng Q FAU - Lau, Wan Y AU - Lau WY FAU - Wang, Xuehao AU - Wang X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070607 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Antibodies) RN - 0 (Interleukin-18) RN - 0 (Mitogens) RN - 0 (RNA, Messenger) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 11028-71-0 (Concanavalin A) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Animals MH - Antibodies/immunology/*pharmacology MH - Apoptosis/drug effects MH - CD4-Positive T-Lymphocytes/drug effects/metabolism/pathology MH - Cell Proliferation/drug effects MH - Concanavalin A MH - Disease Models, Animal MH - Interferon-gamma/genetics/metabolism MH - Interleukin-18/*immunology/*pharmacology MH - Interleukin-4/genetics/metabolism MH - Liver/drug effects/metabolism/pathology MH - Liver Cirrhosis/chemically induced/pathology/*prevention & control MH - Male MH - Matrix Metalloproteinase 2/genetics/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mitogens MH - RNA, Messenger/genetics/metabolism MH - Random Allocation MH - Tissue Inhibitor of Metalloproteinase-1/genetics/metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism EDAT- 2007/06/15 09:00 MHDA- 2007/10/03 09:00 CRDT- 2007/06/15 09:00 PHST- 2006/10/22 00:00 [received] PHST- 2007/01/16 00:00 [revised] PHST- 2007/01/23 00:00 [accepted] PHST- 2007/06/15 09:00 [pubmed] PHST- 2007/10/03 09:00 [medline] PHST- 2007/06/15 09:00 [entrez] AID - S0022-4804(07)00033-9 [pii] AID - 10.1016/j.jss.2007.01.024 [doi] PST - ppublish SO - J Surg Res. 2007 Sep;142(1):175-83. doi: 10.1016/j.jss.2007.01.024. Epub 2007 Jun 7.