Protective effects of a protein-bound polysaccharide, PSK, on Candida albicans infection in mice via tumor necrosis factor-alpha induction.

We investigated the protective mechanism of a protein-bound polysaccharide, PSK, against lethal infection with Candida albicans (C. albicans) in mice. (1) In BALB/c mice inoculated intravenously with C. albicans, the intraperitoneal (ip) administration of PSK increased survival rates and prolonged the survival period depending on the time of administration, the dosage, and the size of fungal inoculum; the maximal effect was obtained when PSK 250 mg/kg was ip administered to mice 24 h before inoculation of 1 x 10(6) C. albicans (30 days survivors showed 60% and the mean survival period of mice with fatal infection increased 209%). (2) The protective effect of PSK was significantly decreased in mice treated with cyclophosphamide or carrageenan, or in mice treated previously with anti-tumor necrosis factor-alpha (TNF-alpha) antibody. (3) The administration of PSK significantly enhanced the expression of TNF-alpha gene in spleen and increased leukocyte functions from 6 h to 1 day after inoculation. (4) When the PSK fraction subjected to hydrolysis with beta1-3 glucanase or hydrazine was used instead of PSK, the anti-fungal activities were significantly decreased. These findings suggested that the protective effect of PSK on lethal C. albicans infection in mice was mainly produced via TNF-alpha functions, and that beta 1-3 glucan and protein moiety in PSK molecule were involved in the expression of the activities.

Effect of a biological response modifier, PSK, on intestinal flora of tumor-bearing mice.

PSK, a protein-bound polysaccharide derived from basidiomycetes, is a biological response modifier that exhibits a variety of activities following oral administration, including prevention of infection. In this study, the effects of oral administration of this drug on microbial flora of tumor-bearing mice were examined. Numbers of Staphylococcus, Streptococcus and Pseudomonas were increased, and those of Bifidobacterium and Lactobacillus were reduced in fresh feces of mice from later than 9 weeks after inoculation of sarcoma 180. However, these changes were prevented by oral administration of PSK. In mice bearing sarcoma 180, the increases in numbers of Staphylococcus and Pseudomonas and the decrease in those of Bifidobacterium were further enhanced by intraperitoneal administration of anticancer agent mitomycin C, but such changes were suppressed by oral administration of PSK. These results suggest that PSK has a preventive effect against abnormal conditions of the intestinal flora induced by tumor inoculation or the administration of anticancer agents.

Effects of PSK on resistance to bacterial infection in splenectomized mice.

Nontumor-bearing C3H/He mice were splenectomized and intravenously inoculated 7 days later with Streptococcus pneumoniae, Pseudomonas aeruginosa, or Escherichia coli. The survival rate was reduced by splenectomy in the animals inoculated with S. pneumoniae, but did not change in those inoculated with P. aeruginosa or E. coli. When splenectomy was performed 2 days after transplantation of X5563, and bacteria were inoculated 7 days after the operation, the survival rate was reduced even in those inoculated with P. aeruginosa or E. coli, and elimination of the bacteria from the blood and liver was delayed. This reduction in resistance to infection was alleviated by oral administration of PSK after the splenectomy.

Influence of PSK (Krestin) on resistance to infection of Pseudomonas aeruginosa in tumor-bearing mice.

C3H/He mice were inoculated with Pseudomonas aeruginosa by various routes 1 day after X5563 transplantation or 4 days after cyclophosphamide (CY) administration. Administration of PSK (Krestin) i.p. or p.o. to the tumor-bearing mice or CY-treated tumor-bearing mice resulted in an increase in survival rates. Viable P. aeruginosa were inoculated i.v. on day 0 into mice inoculated with tumor cells on day -12 and vaccinated with killed P. aeruginosa on day -10, or into mice inoculated with tumor cells on day -15, treated with CY on day -14 and vaccinated on day -10. Resistance to infection, which is enhanced by vaccination, was depressed by tumor burden or treatment with CY, but such depression was prevented by PSK administration.