Antitumor effect of recombinant human interleukin-1 beta alone and in combination with natural human tumor necrosis factor-alpha.

In order to investigate the antitumor effect of recombinant human interleukin-1 beta (IL-1 beta) alone and in combination with natural human tumor necrosis factor-alpha (nHuTNF-alpha), we used female BDF1 mice bearing Lewis lung carcinoma (3LL). IL-1 beta 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 micrograms IL-1 beta/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-1 beta was administered in combination with nHuTNF-alpha, pulmonary metastatic tumors decreased much more than when IL-1 beta was administered alone. When the control group had 18.6 +/- 12.7 metastatic tumors, the nHuTNF-alpha group had 12.3 +/- 3.9 and the IL-1 beta 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-1 beta in combination with nHuTNF-alpha 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-1 beta and TNF-alpha.