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Differential effects of anti-tumor necrosis factor monoclonal antibodies on
systemic inflammatory responses in experimental endotoxemia in chimpanzees
T van der Poll, M Levi, SJ van Deventer, H ten Cate, BL Haagmans, BJ Biemond, HR Buller, CE Hack and JW ten Cate
Center of Hemostasis, Thrombosis, Atherosclerosis, and Inflammation
Research, University of Amsterdam, The Netherlands.
Tumor necrosis factor (TNF) is considered to be a pivotal mediator of
endotoxin-induced lethality. To assess the intermediate role of TNF in
specific systemic inflammatory responses known to contribute to tissue
injury in endotoxemia, eight healthy adult chimpanzees were intravenously
injected with Escherichia coli endotoxin (4 ng/kg). In four of these
animals the administration of endotoxin was followed immediately by a bolus
intravenous injection of an anti-TNF monoclonal antibody (15 mg/kg).
Treatment with anti-TNF completely prevented the endotoxin-induced increase
in serum TNF activity, and profoundly reduced the appearance of
interleukin-6 and -8 (both P < .05). Neutrophilia and lymphopenia were
not affected by anti-TNF, whereas neutrophil degranulation, as measured by
the plasma concentrations of elastase-alpha 1-antitrypsin complexes, was
only slightly reduced (peak levels after endotoxin alone 31.0 +/- 3.4
ng/mL, versus 25.5 +/- 3.4 ng/mL after endotoxin with anti-TNF; P <
.05). Anti-TNF did not influence endotoxin-induced activation of the
coagulation system, as reflected by unchanged increases in the plasma
concentrations of the prothrombin fragment F1 + 2 and thrombin-antithrombin
III complexes. In contrast, anti-TNF strongly attenuated the activation of
the fibrinolytic system, ie, peak plasma levels of plasmin-alpha 2-
antiplasmin were 33.8 +/- 11.1 nmol/L after endotoxin alone and 17.0 +/-
2.9 nmol/L after endotoxin with anti-TNF (P < .05). These results
suggest that TNF is not the common mediator of systemic inflammatory
changes in low-grade endotoxemia. Moreover, the finding that in this mild
model anti-TNF specifically inhibited fibrinolysis suggests that treatment
with anti-TNF potentially may enhance the tendency towards microvascular
thrombosis in sepsis.
Volume 83,
Issue 2,
pp. 446-451,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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[Full Text]
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|
|
|
|
|
|
|
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February 1, 1996;
3(1):
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[Abstract]
[PDF]
|
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|
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