ROLE OF CpG ODN IN CONCANAVALIN A-INDUCED HEPATITIS IN MICE

［Original Article］

ROLE OF CpG ODN IN CONCANAVALIN
A-INDUCED HEPATITIS IN MICE

KAZUMICHI ABE, HIROMASA OHIRA, HIROKO KOBAYASHI,
TSUYOSHI RAI, HIRONOBU SAITO, ATSUSHI TAKAHASHI
and YUKIO SATO

Department of Internal Medicine II, Fukushima Medical University School of Medicine,
Fukushima, 960-1295, Japan

(Received February 10, 2005, accepted March 16, 2005)

Abstract: Objective: To investigate the effects of an intradermal injection of oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs on concanavalin A (Con A)-induced hepatitis, an experimental model of immune-mediated hepatitis.
      Methods: Con A was injected intravenously into Balb/c mice.　Twelve hours after Con A challenge, blood and liver samples were obtained.　CpG ODN was injected intradermally 48 hours before Con A challenge.　The extent of liver injury was assessed by determining serum alanine transaminase (ALT) and by liver histology.　Serum levels of cytokines, including interferon (IFN)-g, tumor necrosis factor (TNF)-a, interleukin (IL)-4 and IL-5, were measured by enzyme-linked immunosorbent assay.
      Results: Co-administration of Con A and CpG ODN significantly increased serum ALT in mice compared with that in the case of administration of Con A alone (10,268±4,654 and 1,140±832 IU/l, respectively, p<0.05).　In liver histology, mice treated with CpG ODN and Con A showed more extensive midzonal necrosis than did mice treated with Con A alone.　These mice also showed significant increases in serum TNF-a and IFN-g and decrease in serum IL-5.
      Conclusions: The results indicate that CpG ODNs aggravate Con A-induced hepatitis by stimulating the production of T-helper-1 (Th1) cytokines, TNF-a and IFN-g, suggesting that bacterial DNA that contains unmethylated CpG motifs may contribute to the exacerbation of immune-mediated liver injury.

Key words: bacterial DNA, autoimmune hepatitis, interferon-g, tumor necrosis factor-a, interleukin-5

阿部和道，大平弘正，小林浩子，雷　　毅，斎藤広信，高橋敦史，佐藤由紀夫

Correspondence to: Hiromasa Ohira, Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan.
E-mail: h-ohira@fmu.ac.jp