The effect of the supernatant of Coley’s mixed bacterial toxin and bacterial lipopolysaccharide on serum levels of IL-10, TGF-β and VEGF, and on survival of tumor-bearing mice -

Abstract

Background: Coley’s Mixed Bacterial Toxin (MBT) was prepared by W. B. Coley in 1893, and used for several years to treat cancer, mainly soft tissue sarcoma. In an earlier study, the effect of MBT, its dialyzed supernatant and its pellet on the levels of IL-12, TNF-α and VEGF was assessed and the active component(s) was (were) reported to be part of the dialyzed supernatant (DS).Aims: The aim of this study was to assess the anti-tumor activity of MBT and its DS on the serum levels of immunosuppressive and angiogenic cytokines in tumor-bearing mice.Methods: MBT and DS were prepared and Lipopolysaccharride (LPS) was used. Four subgroups of C57BL-6 mice were injected intraperitonneally (IP) with B16F10 melanoma cells followed by one injection of RPMI-1640, MBT, LPS or DS. Another four subgroups were injected intraperitoneally with B16F10 melanoma cells followed by three injections at 2 day intervals of RPMI-1640, MBT, LPS or DS. The serum levels of Interleukin-10 (IL-10), Transforming Growth Factor-β (TGF- β) and Vascular Endothelial Growth Factor (VEGF) were determined by ELISA at 2, 4 and 6 hours post- injection. Five mice from each subgroup were monitored for ten days, time of death was noted and survivals were assessed.Results: The levels of IL-10 decreased after one injection of MBT, LPS or DS. Yet, a significant decrease was induced mainly by three injections of LPS or DS. The levels of TGF- β decreased in mice that were treated with one injection of MBT, LPS or DS. However, a considerable decrease was observed in the mice that were given three injections of DS. The levels of VEGF significantly decreased in mice treated with one or three injection of DS. Twenty per cent of the tumor-bearing mice treated with one injection of MBT survived, whereas after three injections of MBT, LPS, or DS there was 20percent, 20percent and 40percent survivals, respectively.Conclusion: The DS appears to contain the active agent(s) responsible for the anti-tumor activity. LPS could be one of the active components. Imp