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Effects on leukocytes after injection of tumor necrosis factor into healthy
humans
T van der Poll, SJ van Deventer, CE Hack, GJ Wolbink, LA Aarden, HR Buller and JW ten Cate
Department of Internal Medicine, University of Amsterdam, The Netherlands.
Tumor necrosis factor (TNF) has been implicated as a proximal mediator of
the septic syndrome. To evaluate the possible role of TNF in leukocyte
activation in septicemia, we performed a cross-over saline- controlled
study in six healthy men who were intravenously injected with recombinant
human TNF (50 micrograms/m2), and analyzed changes in circulating white
blood cells and parameters for neutrophil and monocyte activation. TNF
elicited a very rapid neutropenia, reaching a nadir after 15 minutes,
followed by a neutrophilia. Lymphocytes showed a sustained decrease,
whereas monocytes declined transiently. TNF injection was also associated
with neutrophil activation, as reflected by a mean fivefold increase in the
plasma concentrations of elastase- alpha 1-antitrypsin complexes and a mean
sevenfold increase in plasma lactoferrin levels. Serum neopterin, a marker
of monocyte activation, was significantly increased 24 hours after the
administration of TNF. These changes occurred in the absence of detectable
complement activation, as indicated by unchanged C3a-desarg plasma values.
Serum interleukin-6 showed a nearly 40-fold increase after TNF injection,
whereas interleukin-1 remained undetectable throughout. We conclude that
the systemic release of TNF, triggered early after invasive infection, may
be involved in the alterations in circulating leukocyte numbers and in the
activation of leukocytes, during the development of the septic syndrome.
Volume 79,
Issue 3,
pp. 693-698,
02/01/1992
Copyright © 1992 by The American Society of Hematology
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