title: Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia.
abstract: IL-10 protects mice from LPS-induced lethality. To determine the effects of IL-10 on LPS-induced inflammatory responses, six Papio anubis baboons were i.v. injected with a sublethal dose of LPS (Salmonella typhimurium; 500 microg/kg) directly preceded by either human rIL-10 (n = 3, 500 microg/kg) or diluent (n = 3). IL-10 strongly inhibited LPS-induced release of TNF, IL-6, IL-8, and IL-12 (all p < 0.05). By contrast, IL-10 did neither influence the activation of the coagulation system (plasma levels of thrombin/antithrombin III complexes), nor the activation of the fibrinolytic system (plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor type I, and plasmin/alpha 2-antiplasmin complexes). IL-10 modestly attenuated neutrophilic leukocytosis and neutrophil degranulation (plasma concentrations of elastase/alpha1-antitrypsin complexes) (both p < 0.05). Changes in surface TNF receptor expression on circulating granulocytes were not affected by IL-10. These results suggest that during sublethal endotoxemia the predominant anti-inflammatory effect of IL-10 treatment is inhibition of proinflammatory cytokine release.
authors.affiliation: Cornell University Medical College, Department of Surgery, New York 10021, USA.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: P M
authors.initials: PM
authors.lastname: Jansen
authors.forename: W J
authors.initials: WJ
authors.lastname: Montegut
authors.forename: C C
authors.initials: CC
authors.lastname: Braxton
authors.forename: S E
authors.initials: SE
authors.lastname: Calvano
authors.forename: S A
authors.initials: SA
authors.lastname: Stackpole
authors.forename: S R
authors.initials: SR
authors.lastname: Smith
authors.forename: S W
authors.initials: SW
authors.lastname: Swanson
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
authors.forename: L L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D019446:Endotoxemia / Q000097:blood* / Q000276:immunology* / Q000628:therapy; D005342:Fibrinolysis / Q000187:drug effects / Q000276:immunology; D006098:Granulocytes / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood*; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000008:administration & dosage; D010215:Papio; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016753:Interleukin-10