| Abstract | BACKGROUND/AIM: An understanding of ribavirin's beneficial effects on treatment outcome in chronic hepatitis C (CH-C) may help to develop new treatment approaches. Here we investigated whether ribavirin directly affects HCV-specific reactivity of CD4+T-lymphocytes from patients with CH-C. METHODS: Peripheral blood mononuclear cells from forty HCV RNA positive patients were cultured ex vivo with HCV core, NS3, NS4 alone, and with different concentrations of ribavirin. Virus-specific CD4+ T-cell reactivity was analysed by a proliferation assay; quantitation of cytokine (interferon-gamma, IL-10, IL-5, IL-12p35, IL-12p40) mRNA levels; measurement of interferon-gamma and IL-10 production (by ELISA) and enumeration of interferon-gamma and IL-10 producing T-cells by Elispot assays. RESULTS: At 2-5 microM ribavirin induced de novo or enhanced T-cell proliferation to HCV antigens in a proportion of patients. Increased T-cell proliferation was associated with decreased IL-10 production in response to HCV core and reduced frequency of IL-10 producing CD4+ T-cells, while interferon-gamma levels remained unchanged. At 20 microM ribavirin markedly suppressed T-cell proliferation, and interferon-gamma mRNA expression to HCV antigens. CONCLUSIONS: Ribavirin, at clinically achievable plasma levels, modulates directly the T-cell responses to HCV antigens in some CH-C patients. Suppression of IL-10 production may represent a useful strategy to induce/augment T-cell reactivity to HCV. |
| Authors | Eirini I Rigopoulou, William G H Abbott, Roger Williams, Nikolai V Naoumov
(Affiliation: Institute of Hepatology, University College London, 69-75 Chenies Mews, London WC1E 6HX, UK.)
|
| Journal | Antiviral research
(Antiviral Res)
Vol. 75
Issue 1
Pg. 36-42
(Jul 2007)
ISSN: 0166-3542 Netherlands |
| PMID | 17210188
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antiviral Agents
- Cytokines
- Hepatitis C Antigens
- NS3 protein, hepatitis C virus
- NS4 protein, hepatitis C virus
- Peptide Fragments
- RNA, Messenger
- RNA, Viral
- Viral Core Proteins
- Viral Nonstructural Proteins
- core protein (1-98), hepatitis C virus
- Interleukin-10
- Ribavirin
- Interferon Type II
|
| Topics |
- Antiviral Agents
(therapeutic use)
- CD4-Positive T-Lymphocytes
(drug effects)
- Cell Division
(drug effects)
- Cells, Cultured
- Cytokines
(analysis, genetics, metabolism)
- Dose-Response Relationship, Drug
- Enzyme-Linked Immunosorbent Assay
- Gene Expression
- Hepacivirus
(drug effects)
- Hepatitis C Antigens
(blood)
- Hepatitis C, Chronic
(drug therapy)
- Humans
- Interferon Type II
(analysis, biosynthesis)
- Interleukin-10
(analysis, biosynthesis)
- Peptide Fragments
(metabolism)
- RNA, Messenger
(analysis)
- RNA, Viral
(genetics)
- Ribavirin
(therapeutic use)
- T-Lymphocytes
(drug effects, physiology)
- Viral Core Proteins
(metabolism)
- Viral Nonstructural Proteins
(metabolism)
|
