The therapeutic potential of interleukin-1 beta in the treatment of chemotherapy- or radiation-induced myelosuppression and in tumor therapy.

Abstract

In vivo administration of rHuIL-1 beta selectively enhanced the recovery from granulocytopenia and thrombocytopenia caused by sublethal irradiation or 5-FU treatment. Granulopoiesis and thrombopoiesis were stimulated by rHuIL-1 beta in a dose-dependent manner at doses ranging from 0.1 to 100 micrograms/kg. In this study, we have observed IL-1 to induce at least two distinct types of hematopoietic growth factors in vivo, namely GM-CSF and a thrombopoietin-like factor. Various kinds of CSFs alone did not stimulate colony formation of primitive hematopoietic progenitor cells obtained from 5-FU treated mice. However, the pretreatment of primitive hematopoietic progenitor cells with IL-1 in vitro or in vivo for 5 days accelerated the recovery of a cell population which respond to several types of CSFs. These data suggest that IL-1 may be useful clinically to enhance the recovery of granulocytes and platelets in myelosuppressed patients. In addition, we observed that rHuIL-1 beta is directly cytostatic for certain tumor cells in vitro. Intratumoral or subcutaneous injection of rHuIL-1 beta caused regression of a subcutaneous murine sarcoma by augmenting host antitumor responses. Together with the profound effects on hematopoiesis, these results point to potentially important uses of IL-1 beta in treatment of disease.