Interleukin 10 inhibits the release of CC chemokines during human endotoxemia.
Sixteen healthy subjects were intravenously injected with lipopolysaccharide (LPS), once with placebo and once with recombinant human interleukin (IL)-10 (25 microgram/kg), to determine the effect of IL-10 on LPS-induced production of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1. LPS induced transient increases in serum MIP-1alpha, MIP-1beta, and MCP-1. Pretreatment with IL-10 inhibited LPS-induced release of MIP-1alpha, MIP-1beta, and MCP-1. In whole blood in vitro, the IL-10-induced inhibition of MIP-1alpha and MIP-1beta release was equally potent in the presence or absence of an anti-tumor necrosis factor (TNF) antibody. Although isolated peripheral blood mononuclear cells produced more MIP-1alpha and MIP-1beta than neutrophils, the latter cells were more sensitive to the inhibiting effect of IL-10. IL-10 attenuates LPS-induced production of CC chemokines in human endotoxemia, whereby in vitro experiments suggest that, in the case of MIP-1alpha and MIP-1beta release, this effect is independent from an inhibitory effect on TNF production.
Olszyna
D P
DP
Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. dariuszolszyna@rocketmail.com
Pajkrt
D
D
Lauw
F N
FN
van Deventer
S J
SJ
van Der Poll
T
T
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000097:blood*; D019446:Endotoxemia / Q000139:chemically induced* / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D009504:Neutrophils / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10