Restoration of functional defects in peripheral blood mononuclear cells isolated from cancer patients by thiol antioxidants alpha-lipoic acid and N-acetyl cysteine

The ability of Alpha-Lipoic Acid (ALA) and N-Acetyl Cysteine (NAC), two act ive antioxidant agents, to correct in vitro the most significant functional defects of peripheral blood mononuclear cells (PBMC) isolated from advance d stage cancer patients was studied. The proliferative response of PBMC iso lated from cancer patients to anti-CD3 monoclonal antibody (MAb) and the ex pression of CD25 (IL-2R) and CD95 (Fas) on unstimulated and anti-CD3 MAb-st imulated PBMC were studied, and the serum levels of proinflammatory cytokin es IL-1, IL-6, TNF alpha as markers of pro-cachectic activity in cancer pat ients, and the serum levels of IL-2 and sIL-2R were assessed. Twenty patien ts (mean age 64.6 years) with cancer of long, ovary, endometrium, and head and neck, all in advanced (III, IV) stage of disease, were studied. The ser um levels of IL-1 beta IL-2, IL-6, TNF alpha, and sIL-2R were significantly higher in cancer patients than in normal subjects. The response of PBMC is olated from cancer patients to anti-CD3 MAb was significantly lower than th at of controls. The addition of either ALA 0.001 mM or NAC 0.004 mM in the PBMC cultures stimulated with anti-CD3 MAb significantly increased the resp onse of PBMC isolated from cancer patients and normal subjects. After 24 an d 72 hr of culture with anti-CD3 MAb, the expression of CD25 and CD95 on PB MC isolated from cancer patients was significantly lower than that of PBMC isolated from normal subjects. The addition of either ALA or NAC into cultu res of PBMC isolated from cancer patients significantly increased the perce ntage of cells expressing CD25 as well as those expressing CD95. The result s of the present study show a favorable effect of antioxidant agents ALA an d NAC on several important T-cell functions in vitro in advanced-stage canc er patients. Int. J. Cancer 86:842-847, 2000. (C) 2000 Wiley-Liss, Inc.