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PMID:9847016

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Citation

Hawkins, DL, MacKay, RJ, MacKay, SL and Moldawer, LL (1998) Human interleukin 10 suppresses production of inflammatory mediators by LPS-stimulated equine peritoneal macrophages. Vet. Immunol. Immunopathol. 66:1-10

Abstract

To investigate the ability of recombinant human interleukin 10 (rhuIL-10) to suppress the release of inflammatory mediators from lipopolysaccharide (LPS)-stimulated equine macrophages, rhuIL-10 was added to equine peritoneal macrophage monolayers at concentrations of 0, 0.1, 1, 10, or 100 ng/ml. Thirty minutes later, LPS (E. coli O55:B5) was added at final concentrations of 0, 1, 10, 100 ng/ml. Macrophages were incubated for 16 h at 37 degrees C, then supernates were harvested and assayed for tumor necrosis factor (TNF) activity (L929 cytotoxicity), interleukin-6 (IL-6) activity (B9 proliferation), prostaglandin E2 concentration (ELISA), and nitric oxide (Griess reaction for nitrite). Preincubation of LPS-stimulated peritoneal macrophages with rhuIL-10 caused significant (P<0.05) reduction in secretion of TNF, IL-6, and PGE2, in a dose-dependent manner. Of the inflammatory mediators, TNF was most sensitive to the effects of rhuIL-10. At concentrations of rhuIL-10> or =1 ng/ml, TNF activity in the supernate was inhibited significantly at all concentrations of LPS. At one or more LPS concentrations, there was significant inhibition of each mediator in the presence of 1 ng rhuIL-10/ml and, at 100 ng/ml, rhuIL-10 significantly inhibited production of each mediator at all LPS concentrations tested. When data were expressed as a percentage of control values and pooled across all LPS concentrations, both PGE2 and TNF values were significantly reduced at rhuIL-10 concentrations of > or =1 ng/ml, whereas IL-6 was inhibited significantly at concentrations of > or =10 ng rhuIL-10/ml. Tumor necrosis factor production was more completely suppressed (7.8% of control) by the highest concentration of rhuIL-10(100 ng/ml) than was PGE2 (27.2%) or IL-6 (43.8%). Nitrite was not detected in any supernate from peritoneal macrophage monolayers.

Links

PubMed

Keywords

Animals; Cells, Cultured; Dinoprostone/biosynthesis; Horses/immunology; Horses/metabolism; Humans; Interleukin-10/pharmacology; Interleukin-6/biosynthesis; Lipopolysaccharides/pharmacology; Macrophages, Peritoneal/drug effects; Macrophages, Peritoneal/immunology; Macrophages, Peritoneal/metabolism; Nitric Oxide/biosynthesis; Recombinant Proteins/pharmacology; Tumor Necrosis Factor-alpha/biosynthesis

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:IL10

GO:0060302 : negative regulation of cytokine activity

ECO:0000315:

P

Figures 1-3

complete
CACAO 1998

HUMAN:IL10

GO:0050728: negative regulation of inflammatory response

ECO:0000315:

P

Figures 1-3

complete

HUMAN:IL10

involved_in

GO:0060302: negative regulation of cytokine activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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