Analysis and Examination of Cytokine Interactions by the Median-Effect Model: An Example with Antiviral Action of Tumor Necrosis Factor and Interferon-γ

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Abstract
A mathematical model based on the median effect principle was used to demonstrate its usefulness in studying cytokine interactions. The inhibition of cytopathological effects due to encephalomyocarditis virus (EMCV) by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF) in WISH cells using a microtiter assay was employed. The model was used to analyze the characteristics of the dose-effect relationships of IFN-γ, TNF, and their combination. The method also was used to define synergism as opposed to additive interaction. This application of the median-effect model proved to be easy and accurate and could be useful in the study of interactions in cytokine research.