Role of CpG ODN in concanavalin A-induced hepatitis in mice.
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)-gamma, tumor necrosis factor (TNF)-alpha, 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/1, 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-alpha and IFN-gamma 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-alpha and IFN-gamma, suggesting that bacterial DNA that contains unmethylated CpG motifs may contribute to the exacerbation of immune-mediated liver injury.
Abe
Kazumichi
K
Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
Ohira
Hiromasa
H
Kobayashi
Hiroko
H
Rai
Tsuyoshi
T
Saito
Hironobu
H
Takahashi
Atsushi
A
Sato
Yukio
Y
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003208:Concanavalin A / Q000633:toxicity*; D005260:Female; D006505:Hepatitis / Q000209:etiology* / Q000473:pathology; D007371:Interferon-gamma / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D008099:Liver / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D015848:Interleukin-5; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D000410:Alanine Transaminase