Redox imbalance and immune functions: opposite effects of oxidized low-density lipoproteins and N-acetylcysteine.
This study investigates the in vitro effects of oxidized low-density lipoproteins (ox-LDL), 'physiological' pro-oxidants, N-acetylcysteine (NAC), a free radical scavenger and glutathione precursor, and their combination on human peripheral blood mononuclear cell functions. We found that treatment with ox-LDL induced a significant down-regulation of proliferative response to mitogens, antigens and interleukin-2. Lipid extracts from ox-LDL were able to reproduce the same effect as the lipoprotein. On the other hand, NAC exposure induced a significant up-regulation of proliferative responses to all the stimuli used. Moreover, we showed that natural killer (NK) cell-mediated cytotoxic activity was significantly down-regulated by ox-LDL while treatment with NAC induced a significant up-regulation of NK-cell activity. Finally, we found that ox-LDL and NAC exerted opposite effects on the cytokine network, interfering both at the protein secretion level and the messenger RNA synthesis level. More importantly, when NAC was used in combination with ox-LDL the proliferative responses, NK-cell-mediated cytotoxic activity and cytokine production were restored to values comparable to controls. These data indicate that ox-LDL and NAC modulate immune functions, exerting opposite effects reflecting their pro-oxidant and antioxidant behaviours. Our results add new insights to the key role played by redox imbalance as a modulator of immune system homeostasis and suggest that an antioxidant drug such as NAC could be useful against pathologies associated with an increase in lipid peroxidation.
Viora
M
M
Immunology Department, Istituto Superiore di Sanità, Rome, Italy. viora@iss.it
Quaranta
M G
MG
Straface
E
E
Vari
R
R
Masella
R
R
Malorni
W
W
D000111:Acetylcysteine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens / Q000276:immunology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D008934:Mitogens; D000111:Acetylcysteine