title: Oral Administration of Polymyxin B Modulates the Activity of Lipooligosaccharide E. coli B against Lung Metastases in Murine Tumor Models.
abstract: BACKGROUND
  Polymyxin B (PmB) belongs to the group of cyclic peptide antibiotics, which neutralize the activity of LPS by binding to lipid A. The aim of this study was to analyze the effect of PmB on the biological activity of lipooligosaccharide (LOS E. coli B,rough form of LPS) in vitro and in experimental metastasis models.
  
  
  RESULTS
  Cultures of murine macrophage J774A.1 cells and murine bone marrow-derived dendritic cells (BM-DC) stimulated in vitro with LOS and supplemented with PmB demonstrated a decrease in inflammatory cytokine production (IL-6, IL-10, TNF-α) and down-regulation of CD40, CD80, CD86 and MHC class II molecule expression. Additionally, PmB suspended in drinking water was given to the C57BL/6 mice seven or five days prior to the intravenous injection of B16 or LLC cells and intraperitoneal application of LOS. This strategy of PmB administration was continued throughout the duration of the experiments (29 or 21 days). In B16 model, statistically significant decrease in the number of metastases in mice treated with PmB and LOS (p<0.01) was found on the 14th day of the experiments, whereas the most intensive changes in surface-antigen expression and ex vivo production of IL-6, IL-1β and TNF-α by peritoneal cells were observed 7 days earlier. By contrast, antigen expression and ex vivo production of IL-6, IL-10, IFN-γ by splenocytes remained relatively high and stable. Statistically significant decrease in LLC metastases number was observed after the application of LOS (p<0.01) and in the group of mice preconditioned by PmB and subsequently treated with LOS (LOS + PmB, p<0.01).
  
  
  CONCLUSIONS
  In conclusion, prolonged in vivo application of PmB was not able to neutralize the LOS-induced immune cell activity but its presence in the organism of treated mice was important in modulation of the LOS-mediated response against the development of metastases.
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Jagoda
authors.initials: J
authors.lastname: Kicielińska
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szczygieł
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rossowska
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Anger
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kempińska
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Świtalska
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kaszowska
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Boratyński
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Pajtasz-Piasecka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D003208:Concanavalin A; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000737:chemistry*; D005260:Female; D007275:Injections, Intravenous; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology / Q000556:secondary*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000473:pathology; D008546:Melanoma, Experimental / Q000097:blood / Q000473:pathology; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011112:Polymyxin B / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen / Q000473:pathology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; D003208:Concanavalin A; D011112:Polymyxin B
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