Endotoxin Fever in Granulocytopenic Animals

The febrile response to bacterial endotoxin was measured in rabbits made leukopenic with nitrogen mustard. A striking increase in susceptibility to the lethal effects of endotoxin occurred in severely leukopenic animals. Animals without circulating granulocytes, or with only basophils, developed no significant fever after endotoxin injection. Animals with circulating granulocytes other than basophils exhibited a biphasic febrile response to endotoxin; this response was significantly less in magnitude than that of control animals. Control animals, severely granulocytopenic animals, and animals with no circulating granulocytes other than basophils showed comparable febrile responses to serum pyrogen. These results suggest that granulocytes inactivate endotoxin in vivo and support the hypothesis that leukocyte pyrogen is a necessary intermediate in endotoxin fever. Basophils do not appear to participate in this process. These observations also contradict previous studies that were taken to indicate a normal febrile response to endotoxin in leukopenic animals and suggest that those results are related to the persistence of granulocytes.