Abstract
The antitumor effect of lipopolysaccharides (LPS) has been observed in several experimental models and is likely to be mediated by macrophages. Stimulation of macrophages with LPS results in the release of several cytokines, including tumor necrosis factor, interleukin-1 and neutrophil-activating peptide-1/interleukin-8 (IL-8), which activates polymorphonuclear leukocytes (PMN) in vitro. Since PMN have an antitumor activity, we tested the in vivo effect of IL-8 on the growth of peritoneal carcinomatoses induced by PROb colon cancer cells in syngeneic rat. IL-8 induced a significant regression of tumors measuring 1–5 mm, and a complete regression was observed in 8 out of 40 rats in four independent experiments. IL-8 was not directly cytotoxic in vitro for tumor cells and was effective in vivo in a narrow range of doses. IL-8 had a significant chemotactic effect for peritoneal PMN in both normal and tumor-bearing rats. PMN taken from the peritoneum of tumor-bearing rats during IL-8 treatment had the same cytotoxic activity against PROb tumor cells as PMN from untreated control rats. Microscopic examinations of tumors during the treatment showed poor infiltrating by PMN. We conclude that the antitumor activity of IL-8 in this model is not mediated by PMN cytotoxicity.
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Lagadec P, Jeannin JF, Reisser D, Pelletier H, Olsson O (1987) Treatment with endotoxins of peritoneal carcinomatosis induced by colon tumor cells in the rat. Invasion Metastasis 7: 83
Lagadec P, Jeannin JF, Pelletier H, Reisser D, Olsson O (1989) Involvement of effector cells in the treatment with endotoxins of peritoneal carcinomatosis induced by colon tumour cells. Anti-cancer Res 9: 421
Peveri P, Walz A, Dawald B, Baggiolini M (1988) A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med 167: 1547
Van Damme J, Decock B, Lenaerts JP, Conings R, Bertini R, Mantovani A, Billiau A (1989) Identification by sequence analysis of chemotactic factors for monocytes produced, by normal cells and transformed cells stimulated by virus, double-stranded RNA or cytokine. Eur J Immunol 19: 2367
Van Damme J, Rampart M, Conings R, Decock B, Van Osselaer N, Willems J, Billiau A (1990) The neutrophil activating proteins interleukin 8 and β-thromboglobulin: in vitro and in vivo comparison of NH2-terminally-processed forms. Eur J Immunol 20: 2113
Lindley I, Aschauer H, Seifert JM, Lam C, Brunowski W, Kownatzki E, Thelen M, Peveri P, Dewald B, Tscharner V, Walz A, Baggiolini, M (1988) Synthesis and expression inE. coli of the gene encoding monocyte-derived neutrophil-activating factor: biological equivalence between natural and recombinant neutrophil-activating factor. Proc. Natl Acad Sci USA 85: 9199
Baggiolini M, Walz A, Kunkel SL, (1989) Neutrophil-activating peptide 1/IL-8, a novel cytokine that activates neutrophils. J Clin Invest 84: 1045
Martin F, Caignard, A, Jeannin JF, Leclerc A, Martin M (1983) Selection by trypsin of two sublines of rat colon cancer cells forming progressive or regressive tumors. Int J Cancer 32: 623
Fady C, Reisser D (1989) Newly recruited polymorphonuclear leukocytes are devoid of tumoricidal activity. J Exp Clin Cancer Res 8: 211
Fady C, Reisser D, Martin F (1990) Non-activated rat neutrophils kill syngeneic colon tumor cells by the release of a low molecular weight factor. Immunobiology 181: 1
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55
Weiss J, Slivka A (1982) Monocyte and granulocyte-mediated tumor cell destruction. J Clin Invest 69: 255
Cavallo F, Giovarelli M, Gulino A, Stoppacciaro A, Modesti A, Forni G (1992) Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to non immunogenic murine mammary adenocarcinoma made immunogenic by IL-2 gene. J Immunol 149: 3627
Ribeiro RA, Flores CA, Cunha FQ, Ferreira SH (1991) IL-8 causes in vivo neutrophil migration by a cell-dependent mechanism. Immunology, 73: 472
Mc Call TB, Palmer RM, Moncada S (1991) Induction of nitric oxide synthase in rat peritoneal neutrophils and its inhibition by dexamethasone. Eur J Immunol 21: 2523
Mc Call TB, Palmer RM, Moncada S (1992) Interleukin-8 inhibits the induction of nitric oxide synthase in rat peritoneal neutrophils. Biochem Biophys Res Commun 186, 680
Kudo C, Araki A, Matsushima K, Sendo F (1991) Inhibition of IL-8-induced W3/25+ (CD4+) T lymphocyte recruitment into subcutaneous tissues of rats by selective depletion of in vivo neutrophils with a monoclonal antibody. J Immunol 147: 2196
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Lejeune, P., Reisser, D., Onier, N. et al. Interleukin-8 has antitumor effects in the rat which are not associated with polymorphonuclear leukocyte cytotoxicity. Cancer Immunol Immunother 38, 167–170 (1994). https://doi.org/10.1007/BF01525637
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DOI: https://doi.org/10.1007/BF01525637