Abstract

It has been proposed that the interplay among cytokines derived from T-helper 1 (IFN-γ), T-helper 2 (IL-4) and macrophage (IL-6), is central to the outcome of chronic hepatitis B virus (HBV) infection. To investigate whether there is a difference in the cytokine pattern of responders and non-responders to alpha interferon (α-IFN) therapy, levels of IL-4, IL-6 and IFN-γ were measured by enzyme linked immunosorbent assay in 65 sequential sera taken before, during and up to 2 years (median: 1.5) after α-IFN treatment from 11 children [median age: 5 (3-14); 6 boys] with chronic hepatitis B virus (HBV) infection. All were HBV-DNA/HBeAg positive before treatment. α-IFN dose was 5 MU/m2 3 times per week for 24 weeks. 7 children seroconverted to anti-HBe, 4 did not. Baseline median IL-6 levels were significantly higher among responders [231 (24-395) vs 34 (4.4-106), p<0.001] whilst non responders had higher levels of IFN-γ [187 (98-373) vs 39 (11-442), p<0.001] and IL-4 [263 (5-335) vs 90 (30-576), p<0.001]. During α-IFN treatment, the IL-6 levels increased from 2 to 30 times (median: 16x) the baseline values in patients who responded to α-IFN therapy, reaching a peak just before anti-HBe seroconversion whilst little or no change in the IL-6 levels were observed amongst the patients who did not lose HBeAg. α-IFN therapy did not enhance the production of IL-4 IFN-γ either in responders or non-responders. There was no correlation between cytokine levels and AST. Our findings suggest that IL-6 may contribute to HBV clearance during α-IFN treatment and may have therapeutic potential.

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