Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

Figure 6

Secreted cytokine profiles of KC activated with supernatants of PHH previously incubated with subtoxic concentrations of hepatotoxic drugs. PHH from three donors (A, B, and C; see Table 1) were treated with 100 μM acetaminophen (APAP) or 100 μM diclofenac (DIC) for 1 h. The supernatants were used to stimulate KC from the same donor for 2 h. Inflammatory reactions of KC due to hepatocyte stress/damage were determined by cytokine analysis in KC supernatants. IL-6 ((a1), (b1), and (c1)), TNF-alpha ((a2), (b2), and (c2)), IL-10 ((a3), (b3), and (c3)), and PGE-2 ((a4), (b4), and (c4)) were investigated using cytokine ELISAs. Data are shown as box plots, representing the median, the interquartile range, and minimum and maximum values, .

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(b)

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