title: Induction of cytolytic activity and interferon-gamma production in murine natural killer cells by polymyxins B and E.
abstract: Natural killer (NK) cells are the primary effector cells of the innate immune system and have well-established roles in tumor rejection and resistance to viruses, bacteria and certain parasites. There is a need for more specific immune modulators of NK cell activity that lack the wide-ranging side effects of NK cell-stimulatory interleukins. The polycationic antibiotic polymyxin B (PMB) has been shown to have a unique ability to enhance activities of some immune cells, independent of its antibiotic properties. Here we report that both PMB and its analog polymyxin E (PME) markedly enhanced the activity of NK cells enriched from the murine spleen. Maximal activation of NK cell activity was obtained after 24 h of incubation with PMB at a dose of 300 mug/ml. PMB nonapeptide, one of the two PMB domains, and PME methanesulfonate, the negatively charged derivative of PME, had little effect on NK cell activity. PMB induced interferon (IFN)-gamma and tumor necrosis factor-alpha production in NK cells. Proliferation of NK cells in vitro was significantly stimulated by being incubated with PMB. Administration of PMB to mice for 7 consecutive days stimulated splenic NK cell activity and increased NK cell populations in the spleen. These results suggest that the polycationic antibiotics PMB and PME may up-regulate innate and adaptive immune responses by induction of NK cell activity and IFN-gamma production.
authors.affiliation: Department of Immunochemistry, Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kadota
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Eiichi
authors.initials: E
authors.lastname: Gohda
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011112:Polymyxin B / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D007371:Interferon-gamma; D011112:Polymyxin B; D003091:Colistin