DECREASED NATURAL-KILLER CYTOTOXIC ACTIVITY IN CHRONIC-ALCOHOLISM IS ASSOCIATED WITH ALCOHOL LIVER-DISEASE BUT NOT ACTIVE ETHANOL-CONSUMPTION

Chronic alcohol intake is associated with an increased incidence of ce rtain neoplasms, Natural killer (NK) cells have been considered to be involved in control tumor development and growth, The goal of the pres ent study was to contribute to a better understanding of the effects o f ethanol (EtOH) per se on the NK cell population. Both patients with chronic alcoholism without liver disease (AWLD) and subjects with alco hol-induced cirrhosis (ALC) were carefully selected for this study, Im munophenotypical and functional studies of peripheral blood (PB) NK-ce lls were performed during active EtOH intake and after 3 months of a w ithdrawal period, In the AWLD group a significant increase in number o f NK-cells (CD3-/CD56+) (P < .05) associated with a parallel increase in NK cell lytic activity (P < .01) was observed, In addition, the num ber of cytotoxic T cells displaying the CD3+/CD56+ phenotype as well a s CD8-/CD57+ NK-cell subset was also increased (P < .01 and P < .001, respectively), By contrast, in ALC patients with active EtOH intake (A LCET group), although a significant increase in the number of NK PB ly mphocytes was observed (P < .05), NK lytic activity was depressed (P < .05), suggesting the existence of a decreased lytic activity/NK-cell. After 3 months of EtOH withdrawal, PB mononuclear cells (PBMC) from t he AWLD group patients still displayed an increased NK cytolytic activ ity; in addition, the number of PB NK-cells (CD3-/CD56+ and CD8-/CD57) and CD3+/CD56+ PB T cells continued to be increased, Independently o f the duration of withdrawal period, in ALC patients EtOH withdrawal w as followed by a slight decrease in the NK lytic activity of PBMC with respect to the values in active alcoholism phase; slight differences observed in the NK lytic activity in ALC patients who quit drinking co uld be related to the tendency to decrease of the number of NK cells t oward normal values, Furthermore, although an increase in NK cytotoxic activity after stimulation of PBMC with interleukin-2 (IL-2) was obse rved in ALC, it did not reach the levels observed in healthy subjects. Overall, our results show that the behavior of PB NK-cell population in chronic alcoholism is different according to both the moment of EtO H consumption and the existence or not of ALC. Alcohol by itself induc ed an increase in the number and lytic activity of NK-cells, By contra st, the NK cytolytic activity is constantly depressed in the stage of alcoholic cirrhosis, supporting the notion that immunosurveillance mec hanisms may be affected in these patients.