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Abstract

THE EFFECT OF THE SUPERNATANT OF COLEY’S MIXED BACTERIAL TOXIN (MBT) ON SURVIVAL AND SERUM CYTOKINE LEVELS IN TUMOR-BEARING MICE

Dalal F. Jaber, Nayla S. Al-Akl, Alexander M. Abdelnoor*

Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine and American University of Beirut, Beirut, Lebanon.

ABSTRACT

The anti-tumor activity of Coley’s Mixed Bacterial Toxin (MBT), its dialyzed supernatant (DS) and bacterial lipopolysaccharide (LPS) were assessed by studying their effects on the serum levels of immunosuppressive and angiogenic cytokines in tumor-bearing mice, and their effects on their survival. MBT was prepared and its supernatant was separated and dialyzed (DS). Groups of C57BL/6 mice challenged with B16F10 melanoma cells were treated with either one or 3 injections at 2 day intervals of MBT, DS, LPS or RPMI-1640 (control). 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 in 9 mice in each group. The rest of the mice in each group were monitored for ten days for survival rate assessment. The levels of IL- 10 and TGF-β decreased after one injection of MBT, LPS or DS. Yet, a significant decrease was induced mainly by three injections of DS. The levels of VEGF significantly decreased after one or three injections of DS. Twenty per cent of the tumorbearing mice treated with one injection of MBT survived, whereas after three injections of MBT, LPS, or DS there was 20%, 20% and 40% survivals, respectively. DS appears to contain the active agent(s) responsible for the anti-tumor activity. LPS could be one of the active components. Improved protective and therapeutic results probably could be achieved by increasing the number of multiple doses over a longer period of time.

Keywords: B16F10 tumor cells, anti tumor agents, Lipopolysaccharide, IL-10, TGF-β, VEGF.


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