The therapeutic potential of interleukin-1 beta in the treatment of chemotherapy- or radiation-induced myelosuppression and in tumor therapy.
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.
Nakai
S
S
Cellular Technology Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Hirai
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D001424:Bacterial Infections / Q000276:immunology; D001853:Bone Marrow / Q000528:radiation effects*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004347:Drug Interactions; D006133:Growth Substances / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009369:Neoplasms / Q000628:therapy*; D011878:Radiotherapy / Q000009:adverse effects
D000970:Antineoplastic Agents; D006133:Growth Substances; D007375:Interleukin-1; D007213:Indomethacin