Interaction of interleukin-11 (rhIL-11) with cytotoxic therapies in the human HT-29 colon carcinoma

The cytokine interleukin-11 (rhIL-11) has been shown to enhance the recovery of bone marrow, oral epithelium and intestinal crypt cells after cytotoxic insult by anticancer drugs or ionizing radiation. 5-Fluorouracil based chemotherapy and radiation therapy are frequently used in the treatment of colon cancer. Simultaneous exposure of human HT-29 colon carcinoma cells in culture to rhIL-11 and 5-fluorouracil for 24 h resulted in enhanced cell killing of the HT-29 cells with lower concentrations (1-10 mu M) of 5-fluorouracil compared with the drug alone. Exposure of HT-29 cells to rhIL-11 prior to, during and after radiation delivery did not alter the killing of normally oxygenated or hypoxic HT-29 cells by the radiation. In vivo treatment of nude mice bearing HT-29 colon tumor xenografts with rhIL-11 prior to and during administration of 5-fluorouracil did not alter the killing of the tumor cells or the killing of the bone marrow CFU-GM by the drug. In the tumor growth delay experiments, administration of rhIL-11 to nude mice bearing HT-29 colon tumor xenografts did not alter the growth of the tumor and did not alter the response of the tumor to 5-fluorouracil. However, administration of rhIL-11 to these animals increased the response of the tumor to fractionated radiation therapy resulting in a radiation dose-modifying factor of 1.5+/-0.2. These results indicate that rhIL-11 may be a selective protector of normal tissues without affecting the response of the tumor to therapy.