ABSTRACT
UNLABELLED: AIM OF THIS WORK: Aziridines have been shown to possess marked immunotropic activity. In this study, the in vitro effects of a new aziridine, 2-hydroxy-methyl-1-(N-phtaloyltryptophyl) aziridine, were determined on the proliferative responses of human lymphocytes stimulated by mitogens and on interleukin (IL-2, IL-6) secretion. MATERIAL AND METHODS: Peripheral blood lymphocytes were isolated using differential centrifugation on a density gradient of Ficoll-Paque. They were cultured with or without mitogens (Concanavalin A and lipopolysaccharide), and with different concentrations of the aziridine. Proliferation was monitored by direct cell counts and confirmed by MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. After different incubations, IL-2 and IL-6 were determined by using commercially available Elisa kits. RESULTS: The aziridine tested significantly stimulated the resting and mitogen T and B lymphocyte proliferation at concentrations between 1 microM and 1 mM, in a dose-dependent manner. It also increased IL-2 and IL-6 secretion. CONCLUSION: 2-hydroxy-methyl-1-(N-phtaloyltryptophyl) aziridine displayed immunomodulatory properties and is potentially immunostimulant. It could be used to provide non-specific cell-mediated immune responses.
Subject(s)
Aziridines/pharmacology , Interleukin-2/metabolism , Interleukin-5/metabolism , Lymphocyte Activation/drug effects , Tryptophan/analogs & derivatives , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Cell Separation/methods , Humans , Interleukin-2/blood , Interleukin-5/blood , Lymphocytes/drug effects , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Tryptophan/pharmacologyABSTRACT
Aziridines have been shown to possess marked immunotropic activity. The aim of this work was to study the in vitro effects of different concentrations of three novel aziridines, 2-hydroxy-methyl-1-(N-phtaloylglycyl) aziridine (aziridine 1), 2-hydroxy-methyl-1-(N-phtaloylalanyl) aziridine (aziridine 2) and 2-hydroxy-methyl-1-(N-phtaloylphenylalanyl) aziridine (aziridine 3), on the proliferative responses of human lymphocytes stimulated by mitogens (concanavalin A (Con A) and lipopolysaccharide (LPS)), and interleukin-2 (IL-2), interleukin-6 (IL-6) secretion. The results showed that aziridines 1 and 3 significantly stimulated the resting and Con A or LPS lymphocyte proliferation at concentrations between 1 micromol/l and 1 mmol/l, in a dose-dependent manner, the action of aziridine 3 being the highest. They also increased IL-2 and IL-6 secretion. However, aziridine 2 had no effect on the resting lymphocyte proliferation in the absence of mitogens, at any concentration used, reduced Con A-stimulated T lymphocyte proliferation and LPS- stimulated B lymphocyte proliferation in a dose dependent manner and diminished IL-2 and IL-6 production. None of the three aziridines affected cell viability. In conclusion, the three aziridines used in this study displayed immunomodulatory properties. Aziridines 1 and 3 are potentially immunostimulant while aziridine 2 is immunosuppressive and could be used to provide nonspecific cell-mediated immune responses.