Destruction of tumor cells by monokines released from activated human blood monocytes: evidence for parallel and additive effects of IL-1 and TNF

• Published in: Cancer Immunology Immunotherapy 1988-08, Vol.27 (1), p.7-12
• Main Authors: ICHINOSE, Y, TSAO, J. Y, FIDLER, I. J
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Biological Products - biosynthesis; Biological Products - physiology; Cell Line, Transformed; Cell-Free System; Culture Media; Fibroblasts - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immune Sera - pharmacology; Immunobiology; Interleukin-1 - immunology; Interleukin-1 - pharmacology; Lipopolysaccharides; Macrophage Activation - drug effects; Melanoma - immunology; Mice; Monocytes - immunology; Monocytes - metabolism; Monokines; Organs and cells involved in the immune response; Original; Recombinant Proteins - pharmacology; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/BF00205751

The incubation of human peripheral blood monocytes with endotoxins activates the cells to lyse tumorigenic targets directly and also induces the production and release into the culture medium of factors that produce lysis of mouse-transformed fibroblasts L-929 (tumor necrosis factor (TNF)-sensitive) and human A-375 melanoma cells (interleukin-1 (IL-1)- and TNF-sensitive). Immunoblotting analysis revealed that the culture medium of endotoxin-activated but not of control monocytes contained both IL-1 and TNF with a molecular weight of 17,000 daltons each. TNF activity was determined by lysis of L-929 cells, and IL-1 activity was measured by the proliferation of D-10 cells. The production of IL-1 and TNF was concentration-dependent, and the amounts of these monokines were paralleled. The antitumor activity of the culture supernates from endotoxin-treated monocytes was significantly decreased by incubation with heterologous antisera to IL-1, TNF, or both. Recombinant human IL-1 and TNF were used in parallel experiments and as positive controls. Each monokine used produced cytotoxic effects in susceptible targets. The combination of IL-1 and TNF, which more likely resembles culture supernates of activated macrophages, produced an additive antitumor cytotoxicity effect.