[Activation and regulation of macrophages induced by inoculation of cryodestroyed tumor cells].

Cryosurgery provides two prominent features, that is in situ destruction of malignant tumor and potential immunotherapy against tumor. In order to investigate the immunological response after cryosurgery, immunological system of macrophage activation were studied in an experimental tumor system using BALB/c mice and syngeneic Meth-A fibrosarcoma. The mice inoculated the cryodestroyed Meth-A (Cryo-Meth-A mice) acquired antitumor potency in Meth-A challenge test, and the mice inoculated the Mitomycin C treated Meth-A (MMC-Meth-A mice) also acquired antitumor potency. Spleen cells of Cryo-Meth-A mice showed antitumor activity in Winn assay, and spleen cells of MMC-Meth-A mice also showed antitumor activity. The effector cells in Cryo-Meth-A mice were mainly macrophages and natural killer (NK) cells. On the other hand, they were mainly macrophages and cytotoxic T lymphocytes (CTL) in MMC-Meth-A mice. The maximum macrophage cytostatic activity of Cryo-Meth-A mice was noted on 14 days after inoculation (Day 14), whereas it appeared on Day 7 and continued until Day 14 in MMC-Meth-A mice. Macrophages of Cryo-Meth-A mice enhanced the production activity of interleukin 1 (IL-1), interferon (IFN) and prostaglandin E2 (PGE2). On the other hand, macrophages of MMC-Meth-A mice enhanced production activity of tumor necrosis factor (TNF) and increased Ia antigen positive ratio. These findings suggest that macrophages of both groups are activated by different immunological mechanisms. It was found that Cryo-Meth-A played a role as an alpha-IFN inducer, and the macrophages stimulated with Cryo-Meth-A produced alpha-IFN in vitro. Intraperitoneal (i.p.) administration of the anti-alpha-IFN antibody carried down-regulation of macrophage cytostatic activity and NK activity of Cryo-Meth-A mice, whereas MMC-Meth-A mice were not. In addition to these findings, CTL activity enhanced some extent by i.p. administration of the anti-alpha-IFN antibody. These facts suggest that the alpha-IFN have two ways of immunological regulation, the first one is the activation of macrophage cytostatic activity and NK activity, and the other is down-regulation of CTL activity by suppression of Ia antigen expression of macrophages. These results suggest that cryodestruction changes the tumor antigen of Meth-A cells, thereby Cryo-Meth-A induces peculiar immunological response.