Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia.
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.
van der Poll
T
T
Cornell University Medical College, Department of Surgery, New York 10021, USA.
Jansen
P M
PM
Montegut
W J
WJ
Braxton
C C
CC
Calvano
S E
SE
Stackpole
S A
SA
Smith
S R
SR
Swanson
S W
SW
Hack
C E
CE
Lowry
S F
SF
Moldawer
L L
LL
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
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016753:Interleukin-10