Augmented Antitumor Effect of Recombinant Human Interleukin-1α by Indomethacin

In murine syngeneic tumor models, the antitumor effect of recombinant human interleukin-1α (rHu IL-1α) was significantly augmented by oral coadministration of indomethacin (IND). The augmentation was more or less observed by various routes of rHu IL-1α (i.m., i.v., and intratumoral routes), against various tumors (Meth A sarcoma, colon 26 adenocarcinoma, B16 melanoma, and Lewis lung carcinoma) and irrespective of administration timings (in early and late stages of tumor growth). This result suggests that prostaglandin E₂ produced by host cells in response to rHu IL-1α and/or by tumor mass might interfere with the antitumor activity of rHu IL-1α and also that cyclooxygenase inhibitors such as IND might counteract such interference. In the combination of rHu IL-1α with IND, its efficacious doses (5–50 µg/kg) against murine tumors were at least 300–3000 times lower than its median lethal dose (more than 15 mg/kg). In addition, IND partially prevented the loss of body weight attributed to rHu IL-1α injections at relatively high doses. Combined use of rHu IL-1α with IND seems to be desirable from both therapeutic and toxicological viewpoints.