Effect of splenectomy on hepatic metastasis of colon carcinoma and natural killer activity in the liver

We have previously demonstrated that administration of killed streptococcal preparation (OK432), a biological response modifier, increased the number of asialo GM₁-positive cells in the liver, enhanced NK activity of hepatic mononuclear cells, and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were inoculated into the superior mesenteric vein of C57BL/6 strain mice. In the present study, to clarify the role of the spleen in immune surveillance of the liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on hepatic NK activity has been examined. The number of hepatic metastasis increased in the splenectomized mice, compared with that in sham-operated mice. Administration of OK432 increased the number of asialo GM₁-positive cells in the liver and enhanced NK activity of hepatic mononuclear cells in both groups, but NK activity of hepatic mononuclear cells in the splenectomized mice was less than that of the sham-operated mice. An enhanced NK activity of these cells was abolished by treatment with anti-asialo-GM₁ antibody plus complementin vitro. Interleukin-2 mRNA expression was increased in the spleen 2 hr after OK432 administration and persisted until 8 hr, but was scarcely noted in the liver. On the other hand, NK activity of hepatic mononuclear cells in the asialo GM₁-positive cell-depleted (previous administration of antiserum against asialo GM₁) mice was enhanced after OK432 administration in the sham operated and splenectomized mice, but an enhanced NK activity in these mice was only partially or not at all abolished by treatment with anti-asialo GM₁ antibody plus complementin vitro, respectively. These results suggest that the spleen could play an important role in an immune surveillance of the liver. In addition, OK432 first enhanced NK activity of hepatic mononuclear cells, which are sensitive to the antibody against asialo GM₁. However, when asialo GM₁-positive cells were depleted, OK432 enhanced NK activity of hepatic mononuclear cells, which are resistant to anti-asialo GM₁ serum.