AUGMENTED LOCAL IMMUNITY IN THE LIVER BY A STREPTOCOCCAL PREPARATION,OK432, RELATED TO ANTITUMOR-ACTIVITY OF HEPATIC MACROPHAGES

The aim of this study was to investigate the augmentative effect of a streptococcal preparation, OK432, on the immunological competence of h epatic macrophages. We found that OK432 was distributed predominantly to hepatic macrophages after intravenous injection, and Northern blot analysis revealed that OK432 induced the gene expression of IL-1 alpha , beta, and TNF alpha in the liver. The induction of mRNAs was evident 1 h after the intravenous injection of OK432 and their accumulation r eached a maximal level at 3 h. TNF production of hepatic macrophages w as also increased by the intravenous injection of OK432. Furthermore, OK432 significantly increased the proportion of IL-2 receptor-positive hepatic macrophages. As for antitumor activity in the liver being aug mented by OK432, the cytotoxic and cytostatic activity of hepatic macr ophages from OK432-treated rats against tumor cells was significantly increased and OK432 markedly reduced the number of tumor nodules in th e liver after the inoculation of tumor cells via the portal vein. Thes e findings, which indicate that OK432 has various immune-stimulating a ctions on hepatic macrophages, leading to the augmentation of antitumo r activity in the liver, suggest that OK432 may be of some benefit in helping to prevent hepatic metastasis, at least in part, via its activ ation of hepatic macrophages.