title: In vitro effects of an acyltripeptide, FK565, on NK-cell activity, LAK-cell generation and cytokine production by human mononuclear cells.
abstract: In vitro effects of an immunostimulatory acyltripeptide, FK565, on natural killer (NK)-cell activity, lymphokine-activated killer (LAK)-cell generation and cytokine production of normal human peripheral blood mononuclear cells (MNC) were studied. FK565 used at concentrations ranging from 0.1 to 100 micrograms/ml enhanced NK-cell activity only if adherent MNC were removed. The optimal NK-cell enhancing dose was 2 micrograms/ml FK565. At the same range of concentrations, FK565 activated adherent MNC to induce suppression of NK-cell activity in autologous non-adherent MNC preparations. FK565 also potentiated both the generation of LAK-cell activity in the presence of 1000 U/ml of interleukin 2 (IL2) and the effector phase of LAK cells generated at the IL2 concentration of 50 U/ml. The synergistic interaction of IL2 and FK565 on LAK-cell activity was observed for all drug concentrations used. The effects of FK565 on cytotoxic cells could not be attributed to IL2, interferon gamma or tumor necrosis factor-alpha, because FK565 alone had no detectable influence on in vitro production of these cytokines by MNC. The ability of FK56 to modulate effector cells of natural antitumor immunity indicates that it may have promise as a biological response modifier in humans.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, PA.
authors.forename: Y L
authors.initials: YL
authors.lastname: Wang
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: D
authors.initials: D
authors.lastname: Friberg
authors.forename: R B
authors.initials: RB
authors.lastname: Herberman
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001685:Biological Factors / Q000096:biosynthesis*; D016207:Cytokines; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D001685:Biological Factors; D016207:Cytokines; D007376:Interleukin-2; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine