INTERLEUKIN-8 HAS ANTITUMOR EFFECTS IN THE RAT WHICH ARE NOT ASSOCIATED WITH POLYMORPHONUCLEAR LEUKOCYTE CYTOTOXICITY

The antitumor effect of lipopolysaccharides (LPS) has been observed in several experimental models and is likely to be mediated by macrophag es. Stimulation of macrophages with LPS results in the release of seve ral cytokines, including tumor necrosis factor, interleukin-l and neut rophil-activating peptide-1/interleukin-8 (IL-8), which activates poly morphonuclear leukocytes (PMN) in vitro. Since PMN have an antitumor a ctivity, we tested the in vivo effect of IL-8 on the growth of periton eal carcinomatoses induced by PROb colon cancer cells in syngeneic rat s. IL-8 induced a significant regression of tumors measuring 1-5 mm, a nd a complete regression was observed in 8 out of 40 rats in four inde pendent experiments. IL-8 was not directly cytotoxic in vitro for tumo r 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 an d tumor-bearing rats. PMN taken from the peritoneum of tumor-bearing r ats during IL-8 treatment had the same cytotoxic activity against PROb tumor cells as PMN from untreated control rats. Microscopic examinati ons of tumors during the treatment showed poor infiltrating by PMN. We conclude that the antitumor activity of IL-8 in this model is not med iated by PMN cytotoxicity.