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Activation of the kallikrein-kinin system after endotoxin administration to
normal human volunteers
RA DeLa Cadena, AF Suffredini, JD Page, RA Pixley, N Kaufman, JE Parrillo and RW Colman
Sol Sherry Thrombosis Research Center, Department of Medicine, Temple
University School of Medicine, Philadelphia, PA 19140.
The objective of this study was to determine the role of the kallikrein-
kinin system in healthy humans after intravenous administration of either
Escherichia coli endotoxin or saline. We studied a total of 18 healthy
nonsmoking volunteers, 23 to 38 years old, in an open-label study at the
Critical Care Medicine Department, Clinical Center, National Institutes of
Health (Bethesda, MD) in which some of the patients served as their own
controls. After baseline data collection, the subjects received
intravenously either E coli endotoxin (n = 15, 4 ng/kg of body weight) or
saline (n = 8, controls). Signs, symptoms, systemic blood pressure, factor
XII, plasma prekallikrein (PK), factor XI (FXI), antithrombin III (AT-III),
high molecular weight kininogen (HK), and alpha 2-macroglobulin-kallikrein
complexes were measured at baseline and 1, 2, 3, 5, and 24 hours after
injection of either saline or endotoxin. After infusion of endotoxin, we
found the functional plasma levels of FXI decreased at 2 hours (P < .05)
and at 5 hours (P < .05). Functional PK was significantly depressed by 2
hours (P < .05), at 5 hours (P < .05), and at 24 hours (P < .01),
whereas the PK antigen was only low at 5 hours (P < .05). These changes
were accompanied by a significant increase in circulating alpha
2-macroglobulin-kallikrein complexes at 3 hours (P < .05) and 5 hours (P
< .01). No significant changes occurred in the plasma levels of factor
XII or HK. We concluded that clinical response to intravenous endotoxin in
healthy human volunteers is associated with activation of the
kallikrein-kinin systems. Further investigation is needed with specific
inhibitors of the kallikrein-kinin system to define its primary or
secondary role in the endotoxin-mediated reactions.
Volume 81,
Issue 12,
pp. 3313-3317,
06/15/1993
Copyright © 1993 by The American Society of Hematology
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