Contribution of Granulocytopenia to Endotoxin Sensitivity of Mice Irradiated or Undergoing Graft Versus Host Disease.
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
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Animals compromised by irradiation or graft versus host disease GVHD are highly sensitive to endotoxin ET. In order to determine the causes of the increase in sensitivity in compromised mice, we studied alterations of hepatic central and blood-borne peripheral ET clearance processes. Male B6CBF1 mice were irradiated bilaterally with 1000 rads Co60 at 45 rads per minute. Mice destined to undergo GVHD received 5,000,000 CBA spleen cells i.v. within 4 hours after irradiation. Increased sensitivity to ET, as determined by mortality, occurs shortly after irradiation and correlates with granulocytopenia and thrombocytopenia rather than with impairmant of liver function. It was also found that intestinal ET contributes to mortality of granulocytopenic-thrombocytopenic mice. This was supported by the observation that bacteriologically decontaminated, irradiated animals were 10 times more resistant to challenge with ET than were conventional animals. Thus, an important aspect of increased sensitivity to ET, in compromised mice is defective peripheral clearance.
- Medicine and Medical Research