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‐γ, 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.