BACKGROUND/AIMS: Many patients with chronic hepatitis C are now treated with interferon-alpha (IFN-alpha). The increase in the number of patients treated with IFN-alpha, however, has resulted in increased reports of adverse drug reactions (ADR). This prompted us to investigate for a useful parameter for predicting the effects of IFN-alpha treatment before initiating the therapy for the benefit of patients. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) obtained from patients with chronic hepatitis C and healthy volunteers were incubated at 37 degrees C for 24 hours at various concentrations of IFN-alpha (1, 10(2), and 10(4) IU/ml). The tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) formed in the culture medium were determined. Also, the binding of 125I-labeled IFN-alpha to PBMCs and 2', 5'-oligoadenylate synthetase (2-5AS) activities were measured. RESULTS: The addition of IFN-alpha to PBMCs at concentrations of 1-10(4) IU/ml showed dose-dependent changes in the binding of 125I-labeled IFN-alpha to PBMCs and 2-5AS activities. There was a strong correlation between the production of IL-6 and that of TNF-alpha (r>0.9). The production of IL-6 by the PBMCs of the high responders is significantly higher than that of the low-responders at the same value of TNF-alpha. A statistically significant difference was demonstrated by analysis of covariance. CONCLUSIONS: The findings of this study suggest that two-dimensional analysis of the in vitro production of TNF-alpha and IL-6 by PBMCs induced by IFN-alpha is useful for predicting the outcome of the IFN-alpha treatment in patients.
BACKGROUND/AIMS: Many patients with chronic hepatitis C are now treated with interferon-alpha (IFN-alpha). The increase in the number of patients treated with IFN-alpha, however, has resulted in increased reports of adverse drug reactions (ADR). This prompted us to investigate for a useful parameter for predicting the effects of IFN-alpha treatment before initiating the therapy for the benefit of patients. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) obtained from patients with chronic hepatitis C and healthy volunteers were incubated at 37 degrees C for 24 hours at various concentrations of IFN-alpha (1, 10(2), and 10(4) IU/ml). The tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) formed in the culture medium were determined. Also, the binding of 125I-labeled IFN-alpha to PBMCs and 2', 5'-oligoadenylate synthetase (2-5AS) activities were measured. RESULTS: The addition of IFN-alpha to PBMCs at concentrations of 1-10(4) IU/ml showed dose-dependent changes in the binding of 125I-labeled IFN-alpha to PBMCs and 2-5AS activities. There was a strong correlation between the production of IL-6 and that of TNF-alpha (r>0.9). The production of IL-6 by the PBMCs of the high responders is significantly higher than that of the low-responders at the same value of TNF-alpha. A statistically significant difference was demonstrated by analysis of covariance. CONCLUSIONS: The findings of this study suggest that two-dimensional analysis of the in vitro production of TNF-alpha and IL-6 by PBMCs induced by IFN-alpha is useful for predicting the outcome of the IFN-alpha treatment in patients.
Authors: Jason T Blackard; Minhee Kang; Kenneth E Sherman; Margaret James Koziel; Marion G Peters; Raymond T Chung Journal: J Interferon Cytokine Res Date: 2006-11 Impact factor: 2.607