Oxygen radical scavengers selectively inhibit interleukin 8 production in human whole blood.
The hydroxyl radical (OH.) scavenger dimethyl sulfoxide (DMSO) was found to dose-dependently inhibit interleukin 8 (IL-8) production in LPS-stimulated human whole blood. At a concentration of 1% (vol/vol), DMSO blocked IL-8 release by approximately 90% in the presence of 1 microgram/ml LPS at a 24-h time point, but did not affect cell viability or reduce the production of tumor necrosis factor (TNF), interleukin 6, or interleukin-1 beta (IL-1 beta). DMSO was found to directly inhibit IL-8 expression at the level of transcription. Furthermore, this effect was not LPS-specific, in that IL-8 production was reduced by DMSO to a similar extent upon stimulation of blood with phytohemagglutinin, aggregated immune complexes, TNF, or IL-1 beta. Other oxygen radical scavengers that have been shown to inhibit OH.-dependent reactions (dimethyl thiourea, thiourea, mannitol, and ethanol) also inhibited IL-8 production. Conversely, addition of H2O2 caused a dose-dependent stimulation of IL-8 release. These results provide evidence that reactive oxygen metabolites play an important role in the regulation of IL-8 production and suggest that reduction of IL-8 release may contribute to the beneficial effects of antioxidants in experimental models of inflammation and ischemia/reperfusion injury.
DeForge
L E
LE
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Fantone
J C
JC
Kenney
J S
JS
Remick
D G
DG
D001769:Blood / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D016166:Free Radical Scavengers; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006878:Hydroxides; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis*; D008070:Lipopolysaccharides; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016166:Free Radical Scavengers; D006878:Hydroxides; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D004121:Dimethyl Sulfoxide