1998 Fiscal Year Final Research Report Summary
Treatment for chronic hepatitis C with metallothionein induction by IFN
| Project/Area Number |
08557010
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General medical chemistry
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| Research Institution | Gunma University |
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Principal Investigator |
MORI Masatomo Gunma University School of Medicine, Professor, 医学部, 教授 (80174382)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAMINE Takeaki Gunma University School of Medicine, Professor, 医学部, 教授 (90180520)
SATOH Masao Tokushima Humanities and Sciences, Professor, 薬学部, 教授 (20045743)
SUZUKI Keiji Gunma University School of Medicine, Professor, 医学部, 教授 (40008313)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Metallothionein / Interferon / Hepatitis C / Zinc |
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| Research Abstract |
1. We investigated the reciprocal effects of IL-6, dexamethasone (Dex) and Zn on metallothionein (MT) synthesis in rats. MT synthesis in the liver was induced by 11-6 or Dex, and in an additive manner by a combination of LL-6 and Dex. The increase in liver MT induced by the combination of [L-6 and Dex with Zn was greater than the sum of the increases induced by (1L-6 +Zn) and by (Dex + Zn), suggesting a synergistic increase. The data indicate that the maximal increase in the induction of MT by a combination of IL-6 and Dex depends on an adequate liver Zn content.
2.We studied the effect of IFN on MT induction and HCV clearance in human liver tissue obtained from 16 patients with chronic hepatitis C.Liver histology of 11 patients was improved by IFN therapy from active type to inactive type. Hepatic MT concentration was increased in patients with inactive hepatitis more than in those with active hepatitis. Seven out of 16 patients eradicated HCV from liver tissue by IFN therapy, in whom hepatic MT stains were marked compared to those of HCV positive ones. In addition, MT-mRNA induction in liver was increased in hepatitis C patients treated with IFN and zinc compared with those treated with IFN alone.
3. A pilot study was tried on the effect of combined therapy with IFN and zinc for hepatitis C patients with genotype lb. Fifteen patients were treated by IFN and 160 mg of polaprezinc for 24 weeks. Sixty one patients treated with IEN alone as same schedule served control. At the end of 6 months follow up period, normalization of serum ALT levels(combined group 67%, control 42%) and eradication of HCVRNA(combined group 53%, control 16%) were higher in the patients treated with IEN and zinc than in those treated with IFN alone.
These results suggest MT induction is needed to calm of hepatic inflammation, and therapeutic effect of IFN for hepatitis C may improved in combination with zinc.
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