PROTECTIVE EFFECT OF A PROTEIN-BOUND POLYSACCHARIDE, PSK, ON CLP-INDUCED SEPSIS IN MICE TRANSPLANTED ORTHOTOPICALLY WITH COLON TUMOR

Abstract

We investigated the effects of a protein-bound polysaccharide, PSK, on the resistance of tumor-bearing mice against sepsis induced by cecal ligation and puncture (CLP). (a) In BALB/c mice that had received intracecal transplantation of colon 26 (C26) tumor, CLP with a 21-gauge needle significantly shortened the survival time, compared with that of non-tumor-bearing mice. Oral administration of PSK to such mice resulted in a significant prolongation of the survival time and increase of the survival rates. The effects were dependent on the timing of PSK administration and the dose. (b) CLP significantly increased the IL-10 level in serum, the IL-10 gene expression by spleen cells, the number of IL-10-producing CD4-positive T cells, and the productivity of IL-10 by spleen of tumor-bearing mice compared with that of non-tumor-bearing mice. PSK administration to such mice suppressed the increase. Further, PSK prevented the reduction of gene expression of IFN-gamma and the number of IFN-gamma-producing CD4-positive T cells and IFN-gamma productivity by spleen cells of tumor-bearing CLP-treated mice. (c) Treatment with anti-IFN-gamma monoclonal antibody before CLP significantly reduced the effects of PSK. These findings suggest that the protective effect of PSK on the CLP-induced sepsis in mice transplanted orthotopically with C26 tumor is possibly mediated by suppression of IL-10 and promotion of IFN-gamma.