Comparison of Heinatologic and Febrile Response to Endotoxin in Man

By SHELDON M. WOLFF, MELVIN RUBENSTEIN, JOHN H. MULHOLLAND AND DAVID W. ALLING T HE PROFOUND HEMATOLOGIC alterations evoked in experimental animals following endotoxin administration have been considered to play a major role in the pathogenesis of some of the biologic effects produced by these lipopolysaccharides. Marked leukopenia, primarily granulocytopenia, and subsequent granulocytosis as well as transient thrombocytopenia and hypofibrinogenemia have been reported following endotoxin infusion.25 It has been suggested that a pyrogen released from leukocytes during the granulocytopenic phase is essential for the production of endotoxin fever in experimental animals,6’7 but similar extensive studies in man have not been reported. In addition, the recent demonstration of a linear relationship between endotoxin dose and leukocytic response,8 directs attention to whether a quantitative relationship exists between endotoxin fever and changes in circulating blood cells in man. Since repeated injections render man less susceptible to the febrile effect of endotoxin, a state defined as tolerance, it would be of interest to determine whether or not this diminished febrile effect is also accompanied by decreased leukocytic response. In this report comparisons of hematologic and febrile responses following endotoxin injection in endotoxin nontolerant and tolerant human beings revealed that there was no correlation between leukocytic and febrile response.