title: Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees.
abstract: 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.
authors.affiliation: Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, University of Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: H
authors.initials: H
authors.lastname: ten Cate
authors.forename: S J
authors.initials: SJ
authors.lastname: van Deventer
authors.forename: A J
authors.initials: AJ
authors.lastname: Eerenberg
authors.forename: E R
authors.initials: ER
authors.lastname: de Groot
authors.forename: J
authors.initials: J
authors.lastname: Jansen
authors.forename: H
authors.initials: H
authors.lastname: Gallati
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: 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
chemical_list: 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