Two-dimensional analysis of production of IL-6 and TNF-a can predict the efficacy of IFN-a therapy

BACKGROUND/AIMS: Many patients with chronic hepatitis C are now treated wit h interferon-alpha (IFN-alpha). The increase in the number of patients trea ted with IFN-alpha, however, has resulted in increased reports of adverse d rug reactions (ADR). This prompted us to investigate for a useful parameter for predicting the effects of IFN-alpha treatment before initiating the th erapy for the benefit of patients. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) obtained from patie nts with chronic hepatitis C and healthy volunteers were incubated at 37 de grees 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 I -125-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 I-125-labeled IFN-alpha to PBMCs and 2-5AS activities. There was a strong correlation between the p roduction 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 analys is 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 p atients.