Histopathology and serum acute-phase proteins.

(A) (B) Photomicrographs of small intestine from C57BL/6 control mice (panel A) and SCID mice (panel B) treated with IL-18 plus IL-12 and killed at 72 hours. The small intestinal villi are severely blunted with crypt hyperplasia with abundant apoptotic cells in the crypt epithelium (short arrow). H & E stain at 200 ×. (C) The spleen of a C57BL/6 mouse treated with IL-12 plus IL-18 mice shows atrophy of the lymphoid tissue with abundant apoptotic lymphocytes (long arrow) and reticuloendothelial hyperplasia within the marginal zone (curved arrow). H & E stain, 200 × magnification. (D) Nonadherent splenocytes (85% to 90% NK cells by FACS) from PBS-treated (left panel) or IL-18 plus IL-12–treated SCID mice (right panel) were harvested at 48 hours and analyzed for the presence of apoptotic cells via a flow-cytometric assay using propidium iodide staining.42Apoptotic nuclei appear within the hypodiploid region of the DNA histogram (M1) owing to the endonucleolytic cleavage of DNA. (E) SCID mice received daily injections of IL-18 plus IL-12 or IL-18 alone for 72 hours. Serum was harvested at the indicated time points and analyzed for the presence of α1-acid glycoprotein (right panel) and haptoglobin (left panel) via immunoelectrophoresis. These results represent the mean of duplicate samples ± SEM.