Enhanced antitumor efficacy in mice by combination treatment with interleukin-1 alpha and interferon-alpha

• Published in: Journal of immunotherapy with emphasis on tumor immunology Vol. 15; no. 4; p. 233
• Main Authors: Brunda, M J, Wright, R B, Luistro, L, Harbison, M L, Anderson, T D, McIntyre, K W
• Format: Journal Article
• Language: English
• Published: United States 01.05.1994
• Subjects: Animals; Female; Interferon-alpha - therapeutic use; Interleukin-1 - therapeutic use; Interleukin-6 - blood; Killer Cells, Natural - immunology; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Lymphocyte Activation; Melanoma, Experimental - pathology; Melanoma, Experimental - secondary; Melanoma, Experimental - therapy; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Nude; Recombinant Proteins - therapeutic use; Skin Neoplasms - pathology; Skin Neoplasms - therapy; T-Lymphocytes - immunology; Tumor Cells, Cultured
• ISSN: 1067-5582; 2331-3676
• DOI: 10.1097/00002371-199405000-00001

The antitumor efficacy of recombinant murine interleukin-1 alpha (rMuIL-1 alpha) was evaluated either alone or in combination with recombinant human hybrid interferon alpha A/D (IFN-alpha A/D) against the murine B16 F10 malignant melanoma. Treatment of subcutaneous tumor-bearing mice intraperitoneally with rMuIL-1 alpha resulted in a dose-dependent inhibition of tumor growth with the greatest activity obtained with the maximum tolerated dose of rMuIL-1 alpha (10 micrograms per treatment). Augmented tumor inhibition comparable to that seen in mice treated with a high dose of rMuIL-1 alpha was observed in subcutaneous tumor-bearing mice injected with the combination of IFN-alpha A/D and a low dose of rMuIL-1 alpha. Similar inhibition of subcutaneous tumor growth was obtained in T-cell-deficient nude or natural killer cell-deficient beige mice. In contrast, treatment of mice bearing B16F10 experimental pulmonary metastases with rMuIL-1 alpha resulted in no decrease in the number of metastases, and rMuIL-1 alpha did not potentiate the antimetastatic activity of IFN-alpha A/D. A synergistic induction of IL-6 was induced in mice treated with the combination of rMuIL-1 alpha plus IFN-alpha A/D but the level of IL-6 induced was not correlated with inhibition of tumor growth because this elevation of IL-6 was not observed in tumor-bearing nude mice. No direct antiproliferative activity was demonstrable in vitro against B16 F10 cells with rMuIL-1 alpha, IL-6, or rMuIL-1 alpha plus IL-6, and addition of these cytokines did not enhance the antiproliferative activity of IFN-alpha A/D.