Figure 5.
In vivo activity of SP600125. (a) CD-1 mice were dosed with SP600125 i.v. 15 min before injection with LPS or per os 30 min before injection with LPS. At 90 min, a blood sample was recovered, and the serum was obtained. Samples were analyzed for mouse TNF-α by using an ELISA (BioSource). Results are expressed as the mean and standard error with 4 animals per compound treatment group and 6 animals in vehicle control group. Asterisk (*) indicates P ≤ 0.05. DEX, dexamethasone 21-acetate. (b) Apoptosis in murine thymocytes. Thymocytes were isolated from C57BL/6 mice 48 h after injection with anti-CD3 (50 μg) i.p. and analyzed for CD4 and CD8 by flow cytometry. Control animals received no anti-CD3 or vehicle. SP600125 was administered at 0, 12, 24, and 36 h, 15 mg/kg s.c. Anti-CD3 administration was at a single time immediately after the first dosing of SP600125. Data for double-positive (CD4+ CD8+ ) cells is shown expressed as the mean percentage of total thymocytes (n = 4 per group).