Abstract
Recently it has been recognized that IL-1 plays an important role in hematopoietic regulation. Administration of 5-fluorouracil (5-FU) to mice causes prolonged neutropenia. rHIL-1 injected to mice after 5-FU, accelerated the recovery of hematopoietic progenitors and blood neutrophils. The combination of rhIL-1 and rhG-CSF reduced the neutropenic period significantly. Sublethal irradiation of mice induced profound neutropenia for 3 weeks which was associated with 80% mortality. Administration of rhIL-1 20 hours prior to or 2 hours post irradiation resulted in a significantly improved survival and rapid recovery of the neutrophil count. IL-1 administered alone or in combination with other colony stimulating factors to spontaneous breast tumor bearing mice following 5-FU therapy resulted in a rapid recovery of neutrophils, improved survival, and markedly reduced the tumor mass. Experiments in primates demonstrated that rhIL-1 administered to 5-FU treated animals shortened the neutropenic period from 30 to 17 days and increased the number of marrow progenitors responsive to other CSFs. Prolonged administration of IL-1 (14 days) to these animals resulted in a delayed neutrophil recovery as compared to animals receiving short courses of IL-1. rhIL-1 administered to primates receiving marrow grafts after lethal irradiation, did not result in rapid hematopoietic recovery. In humans, studies with CD-34 positive marrow cells showed that IL-1 had a radioprotective effect on a committed and early marrow progenitors. These data show the therapeutic potential of IL-1 in the treatment of chemoradiotherapy induced myelosuppression.
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References
Dinarello CA. Interleukin-1. Review of infectious diseases 1984; 1: 51–95.
Mochizuki DY, Eisenman JR, Conlon PJ, Larson AD, Tushinski RJ. Proc Natl Acad Sci USA 1987; 84: 5267–71.
Jubinsky PI, Stanley ER. Purification of hematopoietin-1: A multilineage hematopoietic growth factor. Proc natl Acad Sci USA 1985; 82: 2764–7.
Williams DE, Broxmeyer HE. Interleukin-1 alpha enhances thein-vitro survival of purified murine granulocyte-macrophage progenitor cells in the absence of colony stimulating factors. Blood 1988; 72: 1608.
Neta R, Sztein MB, Oppenheim JJ, Gillis S., Douches SD. Thein vivo effects of interleukin 1. I. Bone marrow cells are induced to cycle after administration of interleukin 1. J Immunol 1987; 139: 1861.
Bagby GC., Dinarello CA, Wallace P. Interleukin-1 stimulates granulocyte macrophage colony stimulating activity release by vascular endothelial cells. J Clin Invest 1986; 78: 1316–20.
Zucali JR, Dinarello CA, Olblon DJ, Gross MA, Anderson L, Weiner RS. Interleukin-1 stimulates to produce granulocyte-macrophage colony-stimulating activity and prostaglandin E2. J Clin Invest 1986; 77: 1857–63.
Broudy VC, Kaushansky K, Harlan JM, Adamson JW. Interleukin-1 stimulates human endothelial cells to produce granulocyte-macrophage colony-stimulating factors and granulocyte colony stimulating factors. J Immunol 1987; 139: 464.
Moore MAS., Warren DJ. Interleukin-I and G-CSF synergism:in vivo stimulation of stem cell recovery and hematopoietic regeneration following 5-fluorouracil treatment in mice. Proc Natl Acad Sci USA 1987; 84: 7134–8.
Stork L, Barczuk L, Kissinger M, Robinson W. Interleukin-1 accelerates murine granulocytes following treatment with cyclophosphamide. Blood 1989; 73: 938–44.
Neta R, Oppenheim JJ. Cytokines in therapy of radiation injury. Blood 1988; 72: 1093–5.
Neta R, Douches SD, Oppenheim JJ. Interleukin 1 is a radioprotector. J Immunol 1986; 136: 2483–5.
Morrissey P, Charrier K, Bressler L, Alpert A. The influence of IL-1 treatment on the reconstitution of the hematopoietic and immune systems after sublethal radiation. J Immunol 1988; 140: 4204–10.
Broxmeyer HE. Biomolecule-cell interactions and the regulation of myelopoiesis. Int'l J of Cell Cloning 1986; 4: 378–89.
Pelus LM. Blockade of prostaglandin biosynthesis in intact mice dramatically augments the expansion of committed myeloid progenitor cells (CFU-GM) following acute administration of recombinant human interleukin 1. Submitted.
Dinarello CA, Savage N. Interleukin-1 and its receptor. Critical Reviews in Immunology 1989; 9: 1–20.
Laver J, Ebell W, Castro-Malaspina H. Radiobiological properties of the human hematopoietic microenvironment: Contrasting sensitivities of proliferative capacity and hematopoietic function toin vitro irradiation. Blood 1986; 67: 1090–7.
Iscove NN, Guilbert LJ, Weyman C. Complete replacement of serum in primary cultures of erythropoietin-dependent red cell precursors (CFU-E) by albumin, transferrin, iron, unsaturated fatty acids, lecithin, and cholesterol. Exp Cell Res 1980; 126: 121–7.
Laver J, Moore MAS. Clinical utility of hematopoietic growth factors. JNCI, in press.
Gasparetto C, Laver J, Abboud M, Gillio A, Smith C, O'Reilly RJ, Moore MAS. Effects of IL-1 on hematopoietic progenitors: Evidence of stimulatory and inhibitory activities in a primate model. Blood 1989; 74: 547–50.
Moreb J. Zucali JR, Gross MA, Weiner RS. Protective effects of IL-1 on human hematopoietic progenitor cells treated in vitro with 4-hydroperoxycyclophosphamide. J Immunol 1989; 142-1937–42.
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Laver, J., Abboud, M., Gasparetto, C. et al. Effects of IL-1 on hematopoietic progenitors after myelosuppressive chemoradiotherapy. Biotherapy 1, 293–300 (1989). https://doi.org/10.1007/BF02171005
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DOI: https://doi.org/10.1007/BF02171005