Aseptic endotoxemia in radiation injury and graft-vs-host disease

Endotoxemia of intestinal origin may occur in individuals subjected to high doses of either ionizing radiation or radiation followed by transplants of foreign immune competent cells capable of producing graft-vs-host disease (GVHD). The results of the following studies support the contention that aseptic endotoxemia may be due to failure to clear endotoxin from the circulation and detoxify it in the liver of immunosuppressed animals. To determine if intestinal endotoxin may contribute to pathogenesis in immunosuppressed individuals, B6CBF1 mice were exposed to 850 rads x rays, and transplanted with allogeneic CBA spleen cells. Aseptic endotoxemia, detected with the limulus lysate assay, was found at 24 and 72 hr postirradiation in livers of mice irradiated only. Contrary to this, endotoxin was not found in mice on days 5, 7, and 8 after x irradiation. Mice died between 11 and 13 days after radiation exposure, at which time bacteria and endotoxin were detected in the liver. In contrast, endotoxin was demonstrable on days 1 and 5 in mice undergoing GVHD. Mice receiving allogeneic grafts after 850 rads survived only 7 days, while gram-negative organisms were detected frequently in liver fragments from 24 hr to day 7. By day 4, hepatosplenic localization of iv-injected (51Cr)endotoxin was reduced 50 percent in these animals and 2- to 3-fold increases in endotoxin levels were found in lung, kidney, heart, and brain. Hepatosplenic endotoxin concentration was not altered dramatically in mice receiving radiation alone. Endotoxin levels in other organs were not altered. Thus, endotoxin is present in detectable amounts in the liver of immunosuppressed mice. (U.S.)