Interleukin 1 receptor antagonist inhibits the augmentation of metastasis induced by interleukin 1 or lipopolysaccharide in a human melanoma/nude mouse system

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 20; pp. 5051 - 5054
• Main Authors: CHIRIVI, R. G. S, GAROFALO, A, PADURA, M, MANTOVANI, A, GIAVAZZI, R
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-10-1993
• Subjects: Animals; Anticarcinogenic Agents - therapeutic use; Biological and medical sciences; Cell Line; Dissemination; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - toxicity; Lipopolysaccharides - toxicity; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Medical sciences; Melanoma - pathology; Mice; Mice, Nude; Neoplasm Metastasis - prevention & control; Recombinant Proteins - therapeutic use; Recombinant Proteins - toxicity; Sialoglycoproteins - therapeutic use; Transplantation, Heterologous; Tumor cell; Tumor Cells, Cultured; Tumors; Antineoplastic agent; Animal model; Intravenous administration; Cytokine; Antimetastatic agent; Metastasis; Potential; Malignant tumor; In vitro; In vivo; Treatment; Immunotherapy; Interleukin 1; Established cell line; Metastatic; Antagonist; Inhibition; Tumor cell; Biological receptor
• ISSN: 0008-5472; 1538-7445

This study examined the ability of the recombinant human interleukin 1 receptor antagonist (IL-1ra) to block interleukin 1 (IL-1)-mediated experimental metastases from the A375M human melanoma. In vivo, IL-1ra administrated at concentrations > or = 200 times IL-1 significantly inhibited the increase in lung colonies induced by IL-1 in nude mice. The response to IL-1 was significantly inhibited when IL-1ra was administered simultaneously with or 1 to 3 h before IL-1. In vitro, the incubation of IL-1-activated endothelial cells with IL-1ra prevented the increase in adhesion of A375M melanoma cells. At the same experimental conditions, IL-1ra inhibited the augmented expression of the intracellular and vascular cell adhesion molecules 1 and E-selectin induced by IL-1 on endothelial cells. Lipopolysaccharide, an IL-1 inducer, increased the number of lung colonies in nude mice. IL-1ra injected with or 1 h after lipopolysaccharide inhibited this augmentation, suggesting a role for host-produced IL-1 in metastasis formation.