Prevention of acute chemotherapy-induced death in mice by recombinant human interleukin 1: Protection from hematological and nonhematological toxicities

Giovanna Damia, Kristin L. Komschlies, Hitoyasu Futami, Timothy Back, M. Eilene Gruys, Dan L. Longo, Jonathan R. Keller, Francis W. Ruscetti, Robert H. Wiltrout

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have demonstrated that interleukin 1 (IL-1) can protect most mice from the acute lethal toxicity mediated by high doses of radiation and/or some chemotherapeutic drugs. The results presented herein demonstrate that the pretreatment of mice with recombinant human interleukin 1α (rhIL-1α) protects mice from the 1ethal effects of several myelotoxic chemotherapeutic drugs, including 5-fluorouracil (5FUra), cyclophosphamide, cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II), and 1,3-bis-(2-chloroethyl)-1-nitrosourea. However, pretreatment with rhIL-1α was not effective against the acute lethal toxicity generated by doxorubicin and cisplatin. The chemoprotective effects appear to be at least partially due to myeloprotection/restoration, since the recovery of myeloid colony-forming units and the total cellularity in the bone marrow and spleen were accelerated in the rhIL-1α-pretreated mice. However, the chemoprotective effects of rhIL-1α are apparently not limited to myeloprotection, since pretreatment with rhIL-1α protects mice against the lethal toxicity of both 5FUra and cyclophosphamide, yet bone marrow transplants rescue mice treated with 5FUra but not those treated with cyclophosphamide. The chemoprotective effects of rhIL-1α may be at least partially indirect, since the efficacy of chemoprotection by rhIL-1α is reduced in athymic mice, and interleukin 6, but not tumor necrosis factor a, can substitute for rhIL-1α in chemoprotection from 5FUra.

Original languageEnglish
Pages (from-to)4082-4089
Number of pages8
JournalCancer Research
Volume52
Issue number15
Publication statusPublished - Aug 1 1992

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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