FIGURE 1.

Altered redox state in periodic fever syndrome model cells and patient monocytes. A, general ROS inhibition leads to decreased IL-1β (left panel) and IL-18 (right panel) secretion in simvastatin-treated cells when stimulated with LPS. The values are representative of four independent experiments. B, ratio of reduced versus oxidized glutathione in THP-1 cells. Simvastatin treatment leads to 50% reduction of ratio, as does the GGPP transferase inhibitor, indicating a more oxidized intracellular environment. The values are averages of five independent experiments. C, oxidative stress indicated by mRNA up-regulation of HO-1 (normalized to β2M). Simvastatin treatment increases oxidative stress and up-regulates HO-1. This can be partly rescued by co-incubation with the antioxidant N-acetylcysteine (NAC). The values are averages of three independent experiments. D and E, example of antioxidant capacity measurements of a single patient with its coupled healthy control. Gating on monocytes (D) and lymphocytes (E) was done using size and granularity. On the background measurements, the slopes are similar, indicating equal ROS production. F, simvastatin treatment leads to reduced antioxidant capacity in THP-1 cells. Shown is the ratio of the fluorescence increase with peroxide treatment divided by the background increase. A higher ratio is increased fluorescence and thus a lower capacity to prevent the probe from becoming oxidized. Each line represents an independent experiment. G, antioxidant capacity of blood monocytes from healthy controls (HC) versus MKD patients. The monocytes from patients have less capacity to clear oxidative stress. H, the difference in antioxidant capacity is specific for monocytes as MKD lymphocytes have a similar antioxidant capacity as healthy controls.