Proinflammatory effects of IL-10 during human endotoxemia.
IL-10 is considered a potent antiinflammatory cytokine that strongly inhibits the production of proinflammatory cytokines. Recent studies have suggested that IL-10 also has immunostimulatory properties on CD4+, CD8+ T cells, and/or NK cells, resulting in increased IFN-gamma production. To determine the effect of IL-10 on IFN-gamma production and related inflammatory responses in humans, 16 healthy subjects received a bolus i.v. injection of LPS (4 ng/kg) in combination with either placebo or recombinant human IL-10 (25 microg/kg), administered just before or 1 h after LPS. IL-10 treatment, particularly when administered after LPS, enhanced LPS-induced IFN-gamma release, as well as the release of the IFN-gamma-dependent chemokines IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma, while inhibiting or not influencing the production of IFN-gamma-inducing cytokines. In addition, IL-10 treatment enhanced activation of CTLs and NK cells after LPS injection, as reflected by increased levels of soluble granzymes. These data indicate that high-dose IL-10 treatment in patients with inflammatory disorders can be associated with undesired proinflammatory effects.
Lauw
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FN
Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. F.N.Lauw@AMC.UVA.NL
Pajkrt
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D
Hack
C E
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Kurimoto
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van Deventer
S J
SJ
van der Poll
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D000328:Adult; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000097:blood; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D003594:Cytoplasmic Granules / Q000201:enzymology; D004311:Double-Blind Method; D019446:Endotoxemia / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D053804:Granzymes; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000097:blood / Q000502:physiology; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D010919:Placebos; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000097:blood; D012995:Solubility
C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D010919:Placebos; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human