Relation of leukocyte and fever responses to bacterial endotoxin

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Abstract
Administration of typhoid vaccine or purified bacterial endotoxin produced leukopenia maximal at 50–60 minutes, followed by a second drop or plateau at 120–140 minutes. These changes were parallel to the known biphasic response and were noted in both capillary and venous blood. The initial decrease affects both granulocytes and lymphocytes; subsequent leukocytosis was due to granulocytosis. Anesthesia abolished the febrile response but did not affect the leukocyte changes. Repeated daily administration of endotoxin produced febrile tolerance characterized predominantly by loss of the second peak with shortening of duration of fever. A similar shortening of duration of leukopenia was noted with development of tolerance. Brief monophasic fever and leukopenia also was noted when a second dose was given 6 hours after the first. These observations support the concept of the central role of leukocytes in endotoxin fever, and suggest that changes in the ability of leukocytes to release pyrogen are concerned with the mechanism of febrile tolerance.

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