Effect of lentinan on the production of migration inhibitory factor induced by syngeneic tumor in mice.

Attempts were made to reveal the mechanism of the inhibitory effect of lentinan on methylcholanthrene-induced transplantable fibrosarcoma (A/Ph.MC.SI) isografts. Since the involvement of a delayed-type hypersensitivity response can be supposed to operate against this syngeneic tumor, the enlargement of regional lymph nodes, the DNA synthesis activity and the migration inhibitory factor producing capacity of the regional lymph-node cells were studied in the control and lentinan-treated, tumor-bearing mice at different times after tumor implantation. The only parameter affected until the first sign of tumor inhibition on the 8th day was the MIF-producing capacity. Regional lymph-node cells in the lentinan-treated mice showed a peak response at this time while practically no MIF was produced by cells of non-treated mice. The early phase of the developing anti-tumor reaction (enlargement of and proliferation in the lymph nodes) was initiated in all recipients but only some of them could reject the tumor in the non-treated animals that rejected the tumors in all cases. It can be supposed that a tumor-induced immunosuppression emerges in the tumor-bearers and can be overcome by lentinan treatment, most likely through enhancement of the MIF production. For measurement of MIF activity a continuously dividing in vitro macrophage-like cell line was established and employed in the micro-wound migration assay.