Quantitative studies of human leukocytic and febrile response to single and repeated doses of purified bacterial endotoxin.

Bacterial endotoxins injected intravenously in small doses into animals and man produce, among other effects, a transient granulocytopenia followed by a marked granulocytosis (1-7). Several comprehensive reviews have recently appeared which deal with the wide spectrum of biologic effects of these substances, including their relationship to the pathogenesis of fever, the development of tolerance to repeated administration, and effects upon host resistance to bacterial infection (5, 8, 9). Recent studies utilizing radioisotopic cell-labeling techniques have increased considerably the understanding of granulocyte kinetics. Athens and his associates estimate the total blood granulocytes in man to be made up of nearly equal compartments of circulating cells and cells marginated and sequestrated within the capillary bed (10). The granulocytic elements in the marrow which are no longer capable of proliferation consist of a reserve of mature cells and cells in various stages of maturation which has been estimated to number 20 to 70 times the total blood granulocytes (7, 11, 12). Craddock, Perry and Lawrence consider this marrow granulocyte reserve to be the source of the granulocytes that enter the circulation in response to leukocytopheresis (11) and endotoxin (1). Athens and co-workers have added evidence that the source of the endotoxin granulocytosis is the bone marrow (10). No appreciable return of granulocytes to the circulation from extravascular spaces has been demonstrated. Craddock and others have suggested that the magnitude of the increase in circulating granulocytes after endotoxin administration may relate directly to the size of the marrow granulocyte reserve and