Antitumor Effect of Recombinant Human Interleukin‐1β Alone and in Combination with Natural Human Tumor Necrosis Factor‐α

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 BDF(1) 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 GM(1) antibody and carrageenan. The number of metastatic tumors was increased from 8.9 ± 8.0 to 18.8 ± 11.4 by anti‐asialo GM(1) antibody and from 9.5 ± 6.8 to 28.0 ± 12.3 by carrageenan. It was suggested that asialo GM(1)‐positive cells and macrophage were two of the most important effectors of the antiproliferative effect of IL‐1β and TNF‐α.