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Canine interleukin-18 induces apoptosis and enhances Fas ligand mRNA expression in a canine carcinoma cell line.

Recombinant canine interleukin-18 (IL-18) induced apoptosis in vitro in a canine cancer cell line derived from canine mammary gland tumor tissue as determined by electrophoretical DNA separation and flow cytometry after propidium iodine staining. To investigate Fas ligand (FasL) expression on the cell line, we cloned the partial sequence of canine Fas Ligand (FasL) cDNA from canine lymphocytes. We found, by RT-PCR analyses, that the cell line expressed FasL mRNA and it was augmented by treatment with canine IL-18 and further enhanced by addition of canine IL-12. Treatment with recombinant canine IL-18 resulted in complete regression of the cell line transplanted into scid mice. This anti-tumor activity was not blocked by anti-mouse IFN-gamma and anti-asialo GM1 antibody, suggesting that the tumor regression was not dependent on IFN-gamma or NK cells of the host. Because there is no cross-reactivity of canine IL-18 with mouse host cells, these results suggested that canine IL-18 may be able to directly kill the breast cancer cells by inducing apoptosis. Canine IL-18 should prove useful as an anti-cancer agent.