OXIDIZED LIPOPROTEINS INCLUDING HDL AND THEIR LIPID-PEROXIDATION PRODUCTS INHIBIT TNF-ALPHA SECRETION BY THP-1 HUMAN MACROPHAGES

It has been established that oxidized LDL (ox-LDL) modifies cytokine s ecretion by macrophages, for example, by reducing tumor necrosis facto r 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 wi th that of ox-LDL and some products of oxidation (hydroperoxides and a ldehydes) on the secretion of TNF-alpha from THP-1 human monocytes der ived macrophages in vitro, HDL2, HDL3 and LDL were oxidized with 10 mu M Cu++ for 12 h and/or 24 h. Native and oxidized HDL and LDL were inc ubated for 24 h with macrophages with or without LPS (10 ng/ml) after which TNF-alpha secretion was measured in the culture medium. Lipid hy droperoxides and apolar aldehydes were also incubated with the cells f or 2 h following which the medium was replaced and TNF-alpha secretion measured after a further 22 h of incubation. An inhibition of TNF-alp ha 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 in hibition 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, he xanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF-alpha secre tion (p <.05). These findings demonstrate that ox-HDL, and some of its lipid peroxidation products, plays a role in the modulation of tile i nflammatory response by macrophages as previously observed for ox-LDL. (C) 1997 Elsevier Science Inc.