Pretreatment of human peripheral blood lymphocytes with interleukin-2 or dexamethasone does not alter their response to Met-Enkephalin in a NK-cytotoxic assay.
The effect of Met-Enkephalin (MENK; 10(-12) - 10(-8) M) on NK-activity of peripheral blood lymphocytes (PBL) after in vitro treatment (18 h, 37 degrees 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 donor-related 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 x 10(-9), 2.5 x 10(-8), 2.5 x 10(-7) M), 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(-9) M) 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.
Martin-Kleiner
I
I
Ruder Bosković Institute, Department of Biology and Medicine, Zagreb, Croatia.
Gabrilovac
J
J
D000293:Adolescent; D000328:Adult; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D004744:Enkephalin, Methionine; D003907:Dexamethasone