title: Cotreatment with interferon-alpha and -gamma reduces liver fibrosis in a rat model.
abstract: Background/Aims: Interferon-alpha is used widely to treat viral hepatitis. Interferon-gamma modulates a system attacking infected cells and also has an anti-fibrotic effect. A treatment with interferon-alpha and -gamma has undergone trials in eliminating hepatitis C virus. We investigated effects of cotreatment in a liver fibrosis model to explore anti-fibrotic effects. Methods: Rats were assigned to groups including normal controls (NC), CCl(4) controls, rat interferon-alpha treatment, rat interferon-gamma treatment, and cotreatment. All groups except normal controls received CCl(4) orally for 8 weeks. At the beginning of the third week of exposure, 6 weeks of treatment were initiated according to interferon group. Digitally analyzed immunohistochemistry, biochemical assays, and Northern analysis were performed. Results: Pixels (x10(5)) per field containing immunoreactive type III collagen (fibrotic density) in CCl(4) controls, interferon-alpha, interferon-gamma, and cotreatment groups respectively were [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]. Liver hydroxyproline content correlated with fibrotic density, and was significantly low in the cotreatment group. Plasma hyaluronate and transaminase were significantly low in cotreatment and interferon-alpha groups. Northern blotting showed lowest mRNA expression for type I collagen, desmin, transforming growth factor (TGF)-beta1, and matrix metalloproteinase-2 mRNA in the cotreatment group; tissue inhibitor of metalloproteinase-1 and -2 mRNAs were significantly low in the interferon-gamma group. Conclusions: Cotreatment can suppress collagen and transforming growth factor-beta1 and has an overall anti-fibrotic effect without exacerbating inflammation.
authors.affiliation: Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama City, Toyama, 930-0194, Japan.
authors.forename: Terumi
authors.initials: T
authors.lastname: Takahara
authors.forename: Kota
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Zhang
authors.forename: Osamu
authors.initials: O
authors.lastname: Ando
authors.forename: Mitsukiyo
authors.initials: M
authors.lastname: Fujii
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yata
authors.forename: Jin
authors.initials: J
authors.lastname: Bo
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.forename: Masami
authors.initials: M
authors.lastname: Minemura
authors.forename: Akiharu
authors.initials: A
authors.lastname: Watanabe