Oxidized lipoproteins including HDL and their lipid peroxidation products inhibit TNF-alpha secretion by THP-1 human macrophages

Free Radic Biol Med. 1997;23(4):658-67. doi: 10.1016/s0891-5849(97)00061-0.


It has been established that oxidized LDL (ox-LDL) modifies cytokine secretion by macrophages, for example, by reducing tumor necrosis factor alpha (TNF-(alpha) m-RNA. However, little is known about the effects of oxidized high density lipoprotein (ox-HDL). This study reports the effects of ox-HDL subfractions 2 and 3 (ox-HDL2, ox-HDL3) compared with that of ox-LDL and some products of oxidation (hydroperoxides and aldehydes) on the secretion of TNF-alpha from THP-1 human monocytes derived macrophages in vitro. HDL2, HDL3 and LDL were oxidized with 10 microM Cu++ for 12 h and/or 24 h. Native and oxidized HDL and LDL were incubated for 24 h with macrophages with or without LPS (10 ng/ml) after which TNF-alpha secretion was measured in the culture medium. Lipid hydroperoxides and apolar aldehydes were also incubated with the cells for 2 h following which the medium was replaced and TNF-alpha secretion measured after a further 22 h of incubation. An inhibition of TNF-alpha by ox-HDL2 (p < .05), ox-HDL3 (p < .05) and ox-LDL (p < .05) from THP-1 macrophages was observed in the presence and absence of LPS. This inhibition remained the same after incubation with ox-HDL 12 h and 24 h. Hydroperoxides of linoleic acid did not modify TNF-alpha secretion by cells while five out of eight aldehydes analyzed (2,4-heptadienal, hexanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF-alpha secretion (p < .05). These findings demonstrate that ox-HDL, and some of its lipid peroxidation products, plays a role in the modulation of the inflammatory response by macrophages as previously observed for ox-LDL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism
  • Aldehydes / pharmacology
  • Cell Line
  • Humans
  • Kinetics
  • Lipid Peroxidation*
  • Lipid Peroxides / metabolism
  • Lipid Peroxides / pharmacology
  • Lipopolysaccharides / pharmacology
  • Lipoproteins / pharmacology*
  • Lipoproteins, HDL / pharmacology*
  • Lipoproteins, HDL2
  • Lipoproteins, HDL3
  • Macrophages / drug effects*
  • Macrophages / physiology*
  • Oxidation-Reduction
  • Tumor Necrosis Factor-alpha / metabolism*


  • Aldehydes
  • Lipid Peroxides
  • Lipopolysaccharides
  • Lipoproteins
  • Lipoproteins, HDL
  • Lipoproteins, HDL2
  • Lipoproteins, HDL3
  • Tumor Necrosis Factor-alpha