Effect of 4-hydroxynonenal, a product of lipid peroxidation, on natural cell mediated cytotoxicity.

Lipid peroxidation of cell membrane yields a variety of final products whose a quantitatively important component is 4-hydroxynonenal (HNE). Previous studies performed in our laboratory suggest that HNE may play a physiological role in the control of cellular proliferation and/or differentiation. This appears to be further supported by our recent findings showing that pre-treatment of K562 cells with a physiological concentration of HNE leads to a marked reduction of susceptibility of NK cells. The observed regulatory effects of HNE on tumor cell growth and susceptibility to natural immune resistance, led us to try to better understand the immunotoxicological properties of this aldehyde. The present study analyses the effects of HNE on NK-mediated cytotoxicity. Treatment of MNC as effector cells with concentrations of HNE ranging from 0.001 to 1 microM for 1 h, did not produce noticeable effects on NK activity. Therefore, this aldehyde at physiological concentrations is able to differentiate tumor cells and to down-regulate target susceptibility to NK effectors from one side. On the other side, it is not able to modify the efficiency of the NK function. Moreover, HNE concentrations higher than 1 microM showed significant and concentration-dependent inhibition of NK activity. However, this effect is reversible and can be antagonized, at least in part, by treatment of effector cells with HNE in combination with beta-interferon.