Interleukin-1α: Its possible roles in cancer therapy

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Abstract
Our studies on recombinant human IL-1α 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-1α (18 kDa) was produced through the expression of the cloned human IL-1α cDNA inEscherichia coli and purified to an endotoxin-free homogeneous polypeptide. The human IL-1α 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-1α 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 myelo suppressed mouse model produced by administering anticancer chemotherapeutic drugs. The myelorestorative effect of IL-1α was observed not only on leukocytes/neutrophils, but also on platelets in myelosuppressed mice. In addition, the human IL-1α markedly augmented dose-dependently resistance of normal and leukopenic mice to various microbial infections. These results suggested that recombinant human IL-1α 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-1α may permit more intensive chemo- and radiation therapies using higher doses. Finally, the antitumor activity of the IL-1α itself may play an important role.