Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees

The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of...

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Bibliographic Details
Published in:The Journal of experimental medicine 1994-04, Vol.179 (4), p.1253-1259
Main Authors: VAN DER POLL, T, HACK, C. E, AARDEN, L. A, TEN CATE, H, VAN DEVENTER, S. J. H, EERENBERG, A. J. M, DE GROOT, E. R, JANSEN, J, GALLATI, H, BÜLLER, H. R, TEN CATE, J. W
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Bacterial diseases
Biological and medical sciences
Blood Coagulation
Cell Count
Endotoxins
Experimental bacterial diseases and models
Fibrin - metabolism
Humans
Infectious diseases
Injections, Intravenous
Interleukin-6 - immunology
Interleukin-6 - physiology
Interleukin-8 - metabolism
Medical sciences
Monocytes - metabolism
Neutrophils - cytology
Neutrophils - metabolism
Pan troglodytes
Receptors, Tumor Necrosis Factor - metabolism
Toxemia - immunology
Tumor Necrosis Factor-alpha - metabolism
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Summary:The role of interleukin 6 (IL-6) in the toxic sequelae of sepsis is controversial. To assess the part of IL-6 in inflammatory responses to endotoxin, we investigated eight chimpanzees after either a bolus intravenous injection of Escherichia coli endotoxin (n = 4; 4 ng/kg) or after the same dose of endotoxin with a simultaneous bolus intravenous injection of an anti-IL-6 mAb (30 mg; n = 4). Anti-IL-6 did not affect the induction of the cytokine network (tumor necrosis factor [TNF], soluble TNF receptors types I and II, and IL-8) by endotoxin, nor did it influence the occurrence of a neutrophilic leukocytosis and neutrophil degranulation, as monitored by the measurement of elastase-alpha 1-antitrypsin complexes. In contrast, anti-IL-6 markedly attenuated endotoxin-induced activation of coagulation, monitored with the plasma levels of the prothrombin fragment F1+2 and thrombin-antithrombin III complexes, whereas activation of fibrinolysis, determined with the plasma concentrations of plasmin-alpha 2-antiplasmin complexes, remained unaltered. We conclude that IL-6 does not have a feedback effect on the release of other cytokines after injection of endotoxin, and that it is not involved in endotoxin-induced neutrophilia or neutrophil degranulation. IL-6 is, however, an important intermediate factor in activation of coagulation in low grade endotoxemia in chimpanzees.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.179.4.1253