Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C.
We studied the relationship between immunological markers such as CD4+ proliferation, cytokines profile and lymphocyte activation markers in patients with chronic hepatitis C, having different responses to interferon (IFN) and ribavirin (RBV) treatment. A prospective study of 20 patients was conducted, six had received IFN-alpha-2b alone and 14 IFN in combination with RBV. The proliferative immune responses of peripheral blood mononuclear cells to hepatitis C virus peptides and the lymphocyte activation markers (CD25+, CD38+ and CD69+) were assessed before treatment, at 1 week, and 1, 3 and 6 months of treatment. Cytokines interleukin (IL)-2, IFN-gamma, IL-4 and IL-10 were determined in supernatants before onset of treatment and at 1 and 6 months thereafter. Stimulation indices (SI) were higher in the sustained responders (SR), in comparison with those with no response (NR), before treatment (5.2 +/- 3.7 to 3.3 +/- 1.9, P = 0.028) and also at 6 months (7.8 +/- 1.9 to 4.1 +/- 1.2, P = 0.021). Patients with SR also had high SI to NS3 when compared with those with transitory response or no response (NR) (4.9 +/- 2.5 and 3.3 +/- 1.1, P = 0.033). At 1 month, SR had higher supernatant IL-2 than those with NR (133.8 +/- 119.2 to 56.0 +/- 89.3 pg/mL, P = 0.023) and lower levels of IL-10 (13.8 +/- 10.1 and 167.1 +/- 272.0 pg/mL, P = 0.023) in response to NS3. Combination therapy induced a higher percentage of the lymphocyte activation markers CD69+ and CD38+. In conclusion, we found that SR is associated with higher CD4+ proliferation particularly in response to the NS3 region, promoting a T-helper (Th)1/Th0 profile of cytokines, and that combination therapy induced a higher percentage of lymphocyte activation than therapy with IFN alone.
Marinho
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RT
Liver Unit, Centre of Gastroenterology, Hospital Santa Maria, Lisbon, Portugal. rui.marinho@mail.telepac.pt
Pinto
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Santos
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Lobos
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Moura
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D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014766:Viremia / Q000188:drug therapy / Q000276:immunology
D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin