AbstractThe effect of Met-Enkephalin (MENK; 10−12- 10−8M) on NK-activity of peripheral blood lymphocytes (PBL) afterin vitrotreatment (18 h, 37°C) was examined in 30 young, healthy male donors. In the group as a whole (n = 30), no significant effect of MENK was detected. At the individual level, 18 of 30 donors (60%) responded to MENK either by mild enhancement (up to 8%, 8 responders), or by mild attenuation (up to 12%, 10 responders) of the basal NK-activity. The effect of MENK was donorrelated regarding the dose-response, E/T ratio, and direction of MENK action. The influence of pretreatment of PBL (1 h) with either graded doses of interleukin-2 (IL-2; 3, 25, 50 U/ml) or dexamethasone (Dex; 2.5×10−9, 2.5×10−8, 2.5×10−7M), on the effect of MENK was also tested. The idea was that pretreatment of PBL would result in predictable, and/or stronger response to MENK. In the group as a whole again no significant effect of MENK was detected on the NK-activity of PBL prestimulated by IL-2 (n = 16), or inhibited by Dex (n = 12). Further, pretreatment of PBL with IL-2/Dex did not significantly alter the intensity of modulation by MENK, which was generally mild. The data obtained have shown that pretreatment of PBL with IL-2 or Dex, regardless of their concentrations, did not significantly alter the frequency of responders to MENK being 50%, 62.5% and 64.3% with 3, 25 or 50 U/ml IL-2, respectively, and 50%, with all concentration of Dex used, as compared to that observed with resting PBL (60%). However, at the individual level physiological concentrations of MENK (10−12- 10−9M) induced enhancement or/and attenuation of the NK-activity pretreated with IL-2/Dex, respectively. The effect of MENK at the individual level was donor-related regarding the dose-response, E/T ratio, and direction of MENK action. Thus, pretreatment of PBL with graded concentrations of IL-2/Dex did not alter the effect of MENK on NK-activity, regarding the frequency and intensity, as well as the direction of modulation: it remained bidirectional, of low intensity, and independent of the grade of PBL preactivation/inhibition, therefore unpredictable.