Interleukin-1 alpha: its possible roles in cancer therapy

Our studies on recombinant human IL-1 alpha polypeptide were summarized with respect to molecular cloning, production, quantitative assay systems, antitumor activity, myelorestorative activity and augmentation of host resistance to infections. Recombinant human IL-1 alpha (18 kDa) was produced through the expression of the cloned human IL-1 alpha cDNA in Escherichia coli and purified to an endotoxin-free homogeneous polypeptide. The human IL-1 alpha inhibited dose-dependently the growth of syngeneic murine tumors transplanted in mice and completely regressed the tumors in some cases, and its antitumor activity was significantly enhanced in combination with indomethacin. The human IL-1 alpha accelerated the recovery of the numbers of peripheral leukocytes and neutrophils in a dose-dependent manner at a dose as low as 10 ng/mouse/day in myelosuppressed mouse model produced by administering anticancer chemotherapeutic drugs. The myelorestorative effect of IL-1 alpha was observed not only on leukocytes/neutrophils, but also on platelets in myelosuppressed mice. In addition, the human IL-1 alpha markedly augmented dose-dependently resistance of normal and leukopenic mice to various microbial infections. These results suggested that recombinant human IL-1 alpha might be useful for cancer therapy from the viewpoints of improving adverse effects such as myelosuppression caused by chemotherapy and/or radiation therapy and preventing infections. In addition, use of IL-1 alpha may permit more intensive chemo- and radiation therapies using higher doses. Finally, the antitumor activity of the IL-1 alpha itself may play an important role.