An in vivo Study of Hepatic and Splenic Interleukin‐lβ mRNA Expression Following Oral PSK or LEM Administration

The effects of orally administered biological response modifiers (BRMs) in preventing postoperative micro liver metastasis of primary colorectal cancer were examined in experimental animals. The twoBRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous experiments, we found that oral administration of PSK or LEM suppressed liver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macrophage activities. In the present study in vivo, using reverse transcriptase‐polymerase chain reaction (RT‐PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrophages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of interleukin (IL)‐1β 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‐β levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibilities: (1) hepatic IL‐1β is potentiated by these agents soon after administration, resulting in activation of liver NK cells or macrophages, or (2) these agents stimulate IL‐β production by liver macrophages, and the produced IL‐lβ activates liver NK cells or liver macrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL‐β by PSK and LEM is involved in the early phases of suppression of micro liver metastases of colorectal cancer.