AN IN-VIVO STUDY OF HEPATIC AND SPLENIC INTERLEUKIN-1-BETA MESSENGER-RNA EXPRESSION FOLLOWING ORAL PSK OR LEM ADMINISTRATION

The effects of orally administered biological response modifiers (BRMs ) in preventing postoperative micro liver metastasis of primary colore ctal cancer were examined in experimental animals. The two BRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous exp eriments, we found that oral administration of PSK or LEM suppressed l iver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macropha ge activities. In the present study in vivo, using reverse transcripta se-polymerase chain reaction (RT-PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrop hages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of i nterleukin (IL)-1 beta expression in the liver and spleen in vivo. Two to six hours after oral administration of PSK or LEM (1 g/kg) to mice , IL-1 beta levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibili ties: (1) hepatic IL-1 beta is potentiated by these agents soon after administration, resulting in activation of liver NIC cells or macropha ges, or (2) these agents stimulate IL-1 beta production by liver macro phages, and the produced IL-1 beta activates liver NK cells or liver m acrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL-1 beta by PSK and LEM is involved in the early phases of suppression of micro liver metastas es of colorectal cancer.