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Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C

2004; Wiley; Volume: 11; Issue: 3 Linguagem: Inglês

10.1111/j.1365-2893.2004.00496.x

1365-2893

Rui Tato Marinho, Ruth Pinto, Maria L. Santos, I.Vila Lobos, Miguel Carneiro de Moura,

Immune Cell Function and Interaction

Summary. 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.