QUANTITATIVE STUDIES OF HUMAN LEUKOCYTIC AND FEBRILE RESPONSE TO SINGLE AND REPEATED DOSES OF PURIFIED BACTERIAL ENDOTOXIN*

Abstract

Studies were conducted in 69 normal volunteers, using Pyrexal, the purified endotoxin of Salmonella abortus equi, (lot 010, A. Wander S. A., Bern, Switzerland). Dosage ranged from 0.05 to 5 mug/kg body weight. A maximal rise in total granulocytes was obtained with .8 mug/kg. Higher doses caused a marked shift to the left with prolonged granulocytosis, and progressive increase in fever, unpleasant side effects and degree of lymphopenia, but no further change in total granulocyte increment. The minimal pyrogenic dose was 0.6 mug/kg. With the repeated administration of a moderately pyrogenic dose, (5 mug/kg), the daily peak granulocytic increment remained uniform, although fever, side effects and the immature granulocyte increment decreased progressively. Preinjection counts declined steadily over the first few days, suggesting that the test material itself might affect granulocyte dynamics. These data may serve as a baseline for clinical use. The variability imposed by altered reactivity to endotoxin, the alteration in granulocyte dynamics caused by this agent, and changing response to repeated dosage must, however, be considered in the interpretation of results.