| Abstract: | In order to investigate the antitumor effect of recombinant human interleukin-1β (IL-1β) alone and in combination with natural human tumor necrosis factor-α (nHuTNF-α), we used female BDF1 mice bearing Lewis lung carcinoma (3LL). IL-1β showed an antiproliferative effect against pulmonary metastatic tumors of 3LL in a dose-dependent manner. We observed 19.6 ± 6.6, 18.6 ± 5.3, 14.1 ± 4.4 and 13.0 ± 6.0 metastatic tumors at doses of 0.5, 1.0, 2.5 and 5.0 μg IL-1β/mouse/day by daily intravenous administration (the number of metastatic tumors of the control group was 26.3 ± 8.2). Similar results were obtained by intraperitoneal administration, but in this case, mice showed a marked decrease of body weight. When IL-1β was administered in combination with nHuTNF-α, pulmonary metastatic tumors decreased much more than when IL-1β was administered alone. When the control group had 18.6 ± 12.7 metastatic tumors, the nHuTNF-α group had 12.3 ± 3.9 and the IL-1β group had 12.8 ± 8.0, the group which was administered both cytokines had a significantly decreased number of 5.6 ± 3.3 metastatic tumors. This antiproliferative effect of IL-1β in combination with nHuTNF-α was reduced by the intravenous administration of anti-asialo GM1 antibody and carrageenan. The number of metastatic tumors was increased from 8.9 ± 8.0 to 18.8 ± 11.4 by anti-asialo GM1 antibody and from 9.5 ± 6.8 to 28.0 ± 12.3 by carrageenan. It was suggested that asialo GM1-positive cells and macrophage were two of the most important effectors of the antiproliferative effect of IL-1β and TNF-α. |
