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 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.
van der Poll
T
T
Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, University of Amsterdam, The Netherlands.
Levi
M
M
Hack
C E
CE
ten Cate
H
H
van Deventer
S J
SJ
Eerenberg
A J
AJ
de Groot
E R
ER
Jansen
J
J
Gallati
H
H
Büller
H R
HR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001777:Blood Coagulation; D002452:Cell Count; D004731:Endotoxins; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000276:immunology / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D002679:Pan troglodytes; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014115:Toxemia / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D015850:Interleukin-6; D016209:Interleukin-8; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli; D005337:Fibrin