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.
Ohkura
M
M
First Department of Surgery, Okayama University Medical School.
Fuchimoto
S
S
Orita
K
K
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007958:Leukocyte Count / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
D000906:Antibodies; D006028:Glycosphingolipids; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D002351:Carrageenan