, Volume 61, Issue 6, pp 338–345 | Cite as

Why clinicians should be interested in Interleukin-3

  • Peter Valent
  • Klaus Geissler
  • Christian Sillaber
  • Klaus Lechner
  • Peter Bettelheim
Leading article


Interleukin-3 (IL-3), a product of activated immune cells has recently been cloned and introduced in preclinical and clinical trials. The biological target-cell spectrum of IL-3 is broad and includes progenitor cells of various hematopoietic lineages as well as multiple stages of stem cell differentiation. IL-3 also induces growth of most primitive hemopoietic progenitors (CFU-blast). Synergistic effects on growth of myeloid cells (i.e. macrophages, eosinophils and blood basophils) are obtained by sequential use of IL-3 and later-acting myelopoietic cytokines. In addition, IL-3 supports terminal maturation, prolonges survival and enhances the functional properties of myeloid cells through high-affinity binding sites. In vivo administration of IL-3 is followed by an increase in peripheral white blood cell counts as well as by an increase in the number of circulating progenitor cells giving rise to mature hemopoietic cells in response to more lineage-restricted growth factors. IL-3 also regulates growth of leukemic cells and primes them to become more sensitive to cell cycle specific cytotoxic drugs. IL-3 apparently represents a novel and unique hemopoietic growth factor. Its clinical use should offer new strategies in the treatment of cytopenia, leukemic disease and in stem cell transplantation.

Key words

Interleukin-3 Hemopoietic stem cells Clinical significance 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Barton BE, Mayer R (1989) IL-3 induces differentiation of bone marrow precursor cells to osteoclast-like cells. J Immunol 143: 3211–3216Google Scholar
  2. 2.
    Berdel WE, Danhauser-Riedl S, Steinhauser G, Winton EF (1989) Various human hematopoietic growth factors (Interleukin-3, GM-CSF, G-CSF) stimulate clonal growth of non hematopoietic tumor cells. Blood 73: 80–83Google Scholar
  3. 3.
    Bergui L, Schena M, Gaidano G, Riva M, Caligaris-Cappio F (1989) Interleukin-3 and interleukin-6 synergistically promote the proliferation and differentiation of malignant plasma cell precursors in multiple myeloma. J Exp Med 170: 613–618Google Scholar
  4. 4.
    Bettelheim P, Muhm M, Valent P, Geissler K, Andreeff M, Haimi J, Sillaber C, Hinterberger W, Vieder L, Schulz G, Lechner K (1990) GM-CSF in combination with cytotoxic chemotherapy in AML patients. Bone Marrow Transpl 6 [Suppl 1]: 127–130Google Scholar
  5. 5.
    Bochner BS, Peachell PT, Brown KE, Schleimer RP (1988) Adherence of human basophils to cultured human umbilical vein endothelial cells. J Clin Invest 81: 1355–1364Google Scholar
  6. 6.
    Bot FJ, Dorssers L, Wagemaker G, Löwenberg B (1988) Stimulating spectrum of human recombinant multi-CSF (IL-3) on human marrow precursors: importance of accessory cells. Blood 71: 1609–1614Google Scholar
  7. 7.
    Bot FJ, van Eijk L, Schipper P, Löwenberg B (1989) Effects of human interleukin-3 on granulocyte colony-forming cells in human bone marrow. Blood 73: 1157–1160Google Scholar
  8. 8.
    Browder TM, Abrams JS, Wong PM, Nienhuis AW (1989) Mechanism of autocrine stimulation in hematopoietic cells producing interleukin-3 after retrovirus-mediated gene transfer. Mol Cell Biol 9: 204–213Google Scholar
  9. 9.
    Broxmeyer HE, Williams DE, Hangoc (1987) Synergistic myelopoietic actions in vivo after administration to mice of combinations of purified natural murine colony-stimulating factor 1, recombinant murine interleukin 3, and recombinant murine granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci USA 84: 3871–3876Google Scholar
  10. 10.
    Broxmeyer HE, Williams DE (1988) The production of myeloid blood cells and their regulation during health and disease. CRC Crit Rev Oncol Hematol 8: 173–226Google Scholar
  11. 11.
    Budel LM, Touw IP, Delwel R, Clark SC, Löwenberg B (1989) Interleukin-3 and granulocyte-monocyte colony-stimulating factor receptors on human acute myelocytic leukemia cells and relationship to the proliferative response. Blood 74: 565–571Google Scholar
  12. 12.
    Cannistra SA, Vellenga E, Groshek P, Rambaldi A, Griffin JD (1988) Human granulocyte-monocyte colony-stimulating factor and interleukin 3 stimulate monocyte cytotoxicity through a tumor necrosis factor-dependent mechanism. Blood 71: 672–676Google Scholar
  13. 13.
    Cannistra SA, Griffin JD (1988) Regulation of the production and function of granulocytes and monocytes. Semin Hematol 25: 173–188Google Scholar
  14. 14.
    Chang JM, Metcalf D, Lang RA, Gonda TJ, Johnson GR (1989) Nonneoplastic hematopoietic myeloproliferative syndrome induced by dysregulated multi-CSF (IL-3) expression. Blood 73: 1487–1497Google Scholar
  15. 15.
    Chen BDM, Mueller M, Olencki T (1988) Interleukin-3 (IL-3) stimulates the clonal growth of pulmonary alveolar macrophage of the mouse: role of IL-3 in the regulation of macrophage production outside the bone marrow. Blood 72: 685–690Google Scholar
  16. 16.
    Clark SC, Kamen R (1987) The human hematopoietic colony-stimulating factors. Science 236: 1229–1237Google Scholar
  17. 17.
    Clark-Lewis I, Schrader JW (1988) Molecular structure and biological activities of P cell-stimulating factor (interleukin 3). Lymphokines 15: 1–37Google Scholar
  18. 18.
    Cuturi MC, Anegon I, Sherman F, Loudon R, Clark SC, Perussia B, Trinchieri G (1989) Production of hemopoietic colony-stimulating factors by human natural killer cells. J Exp Med 169: 569–583Google Scholar
  19. 19.
    Del Rizzo DF, Eskinazi D, Axelrad AA (1990) Interleukin-3 opposes the action of negative regulatory protein (NRP) and of transforming growth factor-β (TGF-β) in their inhibition of DNA synthesis of erythroid stem cell BFU-E. Exp Hematol 18: 138–142Google Scholar
  20. 20.
    Dexter TM (1987) Growth factors involved in haemopoiesis. J Cell Sci 88: 1–6Google Scholar
  21. 21.
    Donahue RE, Seehra J, Metzger M, Lefebvre D, Rock B, Carbone S, Nathan DG, Garnick M, Sehgal PK, Lastonn D, LaVallie E, McCoy J, Schendel PF, Norton C, Turner K, Yang YC, Clark S (1988) Human IL-3 and GM-CSF act synergistically in stimulating hematopoiesis in primates. Science 241: 1820–1823Google Scholar
  22. 22.
    Dy M, Schneider E, Guy-Grand D, Lebel B (1988) Histamine-producing cell-stimulating factor (HCSF) and interleukin 3 (IL-3): their effects on histidine and ornithine decarboxylases. Lymphokines 15: 39–64Google Scholar
  23. 23.
    Emerson SG, Yang YC, Clark SC, Long MW (1988) Human recombinant granulocyte-macrophage colony stimulating factor and interleukin 3 have overlapping but distinct hematopoietic activities. J Clin Invest 82: 1282–1287Google Scholar
  24. 24.
    Ernst TJ, Ritchie AR, Stopak KS, Griffin JD (1989) Human monocytes produce IL-3 in response to stimulation with the calcium ionophore A 23187. Blood 74: 116a [suppl]Google Scholar
  25. 25.
    Fabian I, Bleiberg I, Riklis I, Kletter Y (1987) Enhanced reconstitution of hematopoietic organs in irradiated mice, following their transplantation with bone marrow cells pretreated with recombinant interleukin 3. Exp Hematol 15: 1140–1144Google Scholar
  26. 26.
    Fabian I, Kletter Y, Slavin S (1988) Therapeutic potential of recombinant granulocyte-macrophage-colony-stimulating factor and interleukin-3 in murine B-cell leukemia. Blood 72: 913–918Google Scholar
  27. 27.
    Ganser A, Lindemann A, Seipelt G, Ottmann OG, Eder M, Falk S, Herrmann F, Kaltwasser LP, Meuser P, Klausmann M, Frisch J, Schulz G, Mertelsmann R, Hoelzer D (1990) Effects of human interleukin-3 in aplastic anemia. Blood (in press)Google Scholar
  28. 28.
    Ganser A, Lindemann A, Seipelt G, Ottmann OG, Herrmann F, Eder M, Frisch J, Schulz G, Mertelsmann R, Hoelzer D (1990) Effects of recombinant human interleukin-3 in patients with normal hemopoiesis and in patients with bone marrow failure. Blood 76: 666–676Google Scholar
  29. 29.
    Ganser A, Seipelt G, Lindemann A, Ottmann OG, Falk S, Eder M, Herrmann F, Becher R, Höffken K, Büchner T, Klausmann M, Frisch J, Schulz G, Mertelsmann R, Hoelzer D (1990) Effects of recombinant human interleukin-3 in patients with myelodysplastic syndromes. Blood 76: 455–462Google Scholar
  30. 30.
    Garland JM (1986) Growth, receptors and interleukin 3. Immunol Today 7: 104–105Google Scholar
  31. 31.
    Garnick MB, O'Reilly RJ (1989) Clinical promise of new hematopoietic growth factors: M-CSF, IL-3, IL-6. Hematol/Oncol Clin North Am 3: 495–509Google Scholar
  32. 32.
    Geissler K, Valent P, Mayer P, Liehl E, Hinterberger W, Lechner K, Bettelheim P (1990) Interleukin-3 expands the circulating pool of hemopoietic stem cells in primates, Synergism with granulocyte macrophage colony stimulating factor. Blood 75: 2305–2311Google Scholar
  33. 33.
    Geissler K, Valent P, Bettelheim P, Hinterberger W, Lechner K, Liehl E, Mayer P. In vivo synergism of RhIL-3 and RhIL-6 on thrombocytopoiesis in primates (submitted)Google Scholar
  34. 34.
    Gesner TG, Mufson RA, Norton CR, Turner KJ, Yang YC, Clark SC (1988) Specific binding, internalization, and degradation of human recombinant interleukin-3 by cells of the acute myelogenous, leukemia line, KG-1. J Cell Physiol 136: 493–499Google Scholar
  35. 35.
    Gianni AM, Siena S, Bregni M, Tarella C, Stern AC, Pileri A, Bonadonna G (1989) Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation. Lancet II: 580–585Google Scholar
  36. 36.
    Grimaldi JC, Meeker TC (1989) The t(5;14) chromosomal translocation in a case of acute lymphocytic leukemia joins the interleukin-3 gene to the immunoglobulin heavy chain gene. Blood 73: 2081–2085Google Scholar
  37. 37.
    Guba SC, Stella G, Turka LA, June CH, Thompson CB, Emerson SG (1989) Regulation of interleukin 3 gene induction in normal human T cells. J Clin Invest 84: 1701–1706Google Scholar
  38. 38.
    Halperin DS, Estrov Z, Freedman MH (1989) Diamond-Black-fan anemia: promotion of marrow erythropoiesis in vitro by recombinant interleukin-3. Blood 73: 1168–1174Google Scholar
  39. 39.
    Hancock GE, Kaplan G, Cohn ZA (1988) Keratinocyte growth regulation by the products of immune cells. J Exp Med 168: 1395–1402Google Scholar
  40. 40.
    Hirai K, Morita Y, Misaki Y, Ohta K, Takaishi T, Suzuki S, Motoyoshi K, Miyamoto T (1988) Modulation of human basophil histamine release by hemopoietic growth factors. J Immunol 141: 3958–3964Google Scholar
  41. 41.
    Ihle JN (1988) Immunological regulation of hematopoietic stem cell function by interleukin 3 and its role in leukemogenesis. Lymphokines 15: 127–161Google Scholar
  42. 42.
    Ihle JN, Keller J, Oroszlan S, Henderson LE, Copeland TD, Fitch F, Prystowsky MB, Goldwasser E, Schrader JW, Palaszynski E, Dy M, Lebel B (1983) Biologic properties of homogeneous interleukin 3. J Immunol 131: 282–287Google Scholar
  43. 43.
    Ikebuchi K, Clark SC, Ihle JN, Souza LM, Ogawa M (1988) Granulocyte colony-stimulating factor enhances interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 85: 3445–3449Google Scholar
  44. 44.
    Ikebuchi K, Wong GG, Clark SC, Ihle JN, Hirai Y, Ogawa M (1987) Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 84: 9035–9039Google Scholar
  45. 45.
    Iscove NN, Shaw AR, Keller G (1989) Net increase of pluripotential hematopoietic precursors in suspension culture in response to IL-1 and IL-3. J Immunol 142: 2332–2337Google Scholar
  46. 46.
    Ishibashi T, Burstein SA (1986) Interleukin 3 promotes the differentiation of isolated single megakaryocytes. Blood 67: 1512–1514Google Scholar
  47. 47.
    Itoh N, Yonehara S, Schreurs J, Gorman DM, Maruyama K, Ishii A, Yahara I, Arai KI, Miyajima A (1990) Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family. Science 247: 324–327Google Scholar
  48. 48.
    Kannourakis G, Johnson GR (1990) Proliferative properties of unfractionated, purified, and single cell human progenitor populations simulated by recombinant human interleukin-3. Blood 75: 370–377Google Scholar
  49. 49.
    Kindler V, Thorens B, Vassalli P (1987) In vivo effect of murine recombinant interleukin 3 on early hemopoietic progenitors. Eur J Immunol 17: 1511–1514Google Scholar
  50. 50.
    Kobayashi M, Van Leeuwen BH, Elsbury S, Martinson ME, Young IG, Hapel AJ (1989) Interleukin-3 is significantly more effective than other colony-stimulating factors in long-term maintenance of human bone marrow-derived colony-forming cells in vitro. Blood 73: 1836–1841Google Scholar
  51. 51.
    Koike K, Nakahata T, Takagi M, Kobayashi T, Ishiguro A, Tsuji K, Naganuma K, Okano A, Akiyama Y, Akabane T (1988) Synergism of BSF-2/interleukin-6 and interleukin-3 on development of multipotent hemopoietic progenitors in serum-free culture. J Exp Med 168: 879–890Google Scholar
  52. 52.
    Kurimoto Y, DeWeck AL, Dahinden CA (1989) Interleukin-3 depenent mediator release in basophils triggered by C5a. J Exp Med 170: 467–469Google Scholar
  53. 53.
    Kurzrock R, Talpaz M, Salewski E, Guttermann JU (1990) Phase I Clinical trials with rhu-IL-3 in Hematopoietic growth factors — Clinical update, ASH Symposium on hemopoietic growth factors. Atlanta Georgia, pp 9–11Google Scholar
  54. 54.
    Laver J, Moore MAS (1989) Clinical use of recombinant human hematopoietic growth factors. J Nat Cancer Inst 81: 1370–1382Google Scholar
  55. 55.
    Leary AG, Ikebuchi K, Hirai Y, Wong GG, Yang YC, Clark SC, Ogawa M (1988) Synergism between interleukin-6 and interleukin-3 in supporting proliferation of human hematopoietic stem cells: comparison with interleukin-1 alpha. Blood 71: 1759–1763Google Scholar
  56. 56.
    Leary AG, Yang YC, Clark SC, Gasson JC, Golde DW, Ogawa M (1987) Recombinant gibbon interleukin 3 supports formation of human multilineage colonies and blast cell colonies in culture: comparison with recombinant human granulocyte-macrophage colony-stimulating factor. Blood 70: 1343–1348Google Scholar
  57. 57.
    LeBeau MM, Epstein ND, O'Brien SJ, Nienhuis AW, Yang YC, Clark SC, Rowley JD (1987) The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q. Proc Natl Acad Sci USA 84: 5913–5917Google Scholar
  58. 58.
    Levin J (1989) Is interleukin-3 a physiological regulator of megakaryocytopoiesis, in vivo? Blood Cells 15: 134–139Google Scholar
  59. 59.
    Lista P, Porcu P, Avanzi GC, Pegoraro L (1988) Interleukin 3 enhances the cytotoxic activity of 1-β-D-arabinofuranosyl cytosine (ara-C) on acute myeloblastic leukaemia (AML) cells. Br J Haematol 69: 121–123Google Scholar
  60. 60.
    Lopez AF, To LB, Yang YC, Gamble JR, Shannon MF, Burns GF, Dyson PG, Juttner CA, Clark SC, Vadas MA (1987) Stimulation of proliferation, differentiation, and function of human cells by primate interleukin 3. Proc Natl Acad Sci USA 84: 2761–2765Google Scholar
  61. 61.
    Lopez AF, Eglinton JM, Gillis D, Park LS, Clark S, Vadas MA (1989) Reciprocal inhibition of binding between interleukin-3 and granulocyte-macrophage colony-stimulating factor to human eosinophils. Proc Natl Acad Sci (USA) 86: 7022–7026Google Scholar
  62. 62.
    Lopez AF, Dyson PG, To LB, Elliott MJ, Milton SE, Russell JA, Juttner CA, Yang YC, Clark SC, Vadas MA (1988) Recombinant human interleukin-3 stimulation of hematopoiesis in humans: loss of responsiveness with differentiation in the neutrophilic myeloid series. Blood 72: 1797–1804Google Scholar
  63. 63.
    Lotem J, Sachs L (1988) In vivo control of differentiation of myeloid leukemic cells by recombinant granulocyte-macrophage colony-stimulating factor and interleukin 3. Blood 71: 375–382Google Scholar
  64. 64.
    Mayer P, Valent P, Schmidt G, Liehl E, Bettelheim P (1989) The in vivo effects of recombinant human IL-3: Demonstration of basophil differentiation factor, histamine producing activity and priming of GM-CSF responsive progenitors in non human primates. Blood 74: 613–621Google Scholar
  65. 65.
    McNiece I, Andrews R, Stewart M, Clark S, Boone T, Quesenberry P (1989) Action of interleukin-3, G-CSF, and GM-CSF on highly enriched human hematopoietic progenitor cells: synergistic interaction of GM-CSF plus G-CSF. Blood 74: 110–114Google Scholar
  66. 66.
    Merget RD, Maurer AB, Koch U, Ganser A, Ottmann OG, Schultze-Werninghaus G, Seipelt G, Zachgo W, Hoelzer D, Meier-Sydow J (1990) Histamine release from basophils after in vivo application of recombinant human interleukin-3 in man. Int Arch All Appl Immunol (in press)Google Scholar
  67. 67.
    Messner HA, Yamasaki K, Jamal N, Minden MM, Yang YC, Wong GG, Clark SC (1987) Growth of human hemopoietic colonies in response to recombinant gibbon interleukin 3: comparison with human recombinant granulocyte and granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci USA 84: 6765–6769Google Scholar
  68. 68.
    Metcalf D, Begley CG, Johnson GR, Nicola NA, Lopez AF, Williamson DJ (1986) Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. Blood 68: 46–57Google Scholar
  69. 69.
    Metcalf D, Nicola NA (1988) Tissue localization and fate in mice of injected multipotential colony-stimulating factor. Proc Natl Acad Sci USA 85: 3160–3164Google Scholar
  70. 70.
    Metcalf D (1988) The multipotential colony-stimulating factor, multi-CSF (IL-3). Lymphokines 15: 183–217Google Scholar
  71. 71.
    Metcalf D (1989) The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature 339: 27–30Google Scholar
  72. 72.
    Migliaccio G, Migliaccio AR, Adamson JW (1988) In vitro differentiation of human granulocyte/macrophage and erythroid progenitors: comparative analysis of the influence of recombinant human erythropoietin, G-CSF, GM-CSF, and IL-3 in serum-supplemented and serum-deprived cultures. Blood 72: 248–256Google Scholar
  73. 73.
    Migliaccio G, Migliaccio AR, Visser JWM (1988) Synergism between erythropoietin and interleukin-3 in the induction of hematopoietic stem cell proliferation and erythroid burst colony formation. Blood 72: 944–951Google Scholar
  74. 74.
    Miyauchi J, Kelleher CA, Yang YC, Wong GG, Clark SC, Minden MD, Minkin S, McCulloch EA (1987) The effects of three recombinant growth factors, IL-3, GM-CSF, and G-CSF, on the blast cells of acute myeloblastic leukemia maintained in short-term suspension culture. Blood 70: 657–663Google Scholar
  75. 75.
    Moreb J, Zucali JR, Weiner RS (1989) The role of interleukin 3 and interleukin 6 in the protection from 4-hydroperoxycyclo-phosphamide and the proliferation of early human hematopoietic progenitor cells. Exp Hematol 17: 1022–1027Google Scholar
  76. 76.
    Nicola NA (1987) Why do hemopoietic growth factor receptors interact with each other? Immunol Today 8: 134–139Google Scholar
  77. 77.
    Oster W, Lindemann A, Mertelsmann R, Herrmann F (1989) Granulocyte-macrophage colony-stimulating factor (CSF) and multilineage CSF recruit human monocytes to express granulocyte CSF. Blood 73: 64–67Google Scholar
  78. 78.
    Oster W, Lindemann A, Mertelsmann R, Herrmann F (1988) Regulation of gene expression of M-, G-, GM-, and multi-CSF in normal and malignant hematopoietic cells. Blood Cells 14: 443–462Google Scholar
  79. 79.
    Oster W, Lindemann A, Mertelsmann R, Herrmann F (1989) Production of macrophage-, granulocyte-, granulocyte-macrophage-and multi-colony-stimulating factor by peripheral blood cells. Eur J Immunol 19: 543–547Google Scholar
  80. 80.
    Otsuka T, Miyajima A, Brown N, Otsu K, Abrams J, Saeland S, Caux C, de Waal Malefijt R, de Vries J, Meyerson P, Yokota K, Gemmel L, Rennick D, Lee F, Arai N, Arai KI, Yokota T (1988) Isolation and characterization of an expressible cDNA encoding human IL-3. Induction of IL-3 mRNA in human T cell clones. J Immunol 140: 2288–2295Google Scholar
  81. 81.
    Ottmann OG, Abboud M, Welte K, Souza LM, Pelus LM (1989) Stimulation of human hematopoietic progenitor cell proliferation and differentiation by recombinant human interleukin 3. Comparison and interactions with recombinant human granulocyte-macrophage and granulocyte colony-stimulating factors. Exp Hematol 17: 191–197Google Scholar
  82. 82.
    Ottmann OG, Ganser A, Seipelt G, Eder M, Schulz G, Hoelzer D (1990) Effects of recombinant human interleukin-3 on human hemopoietic progenitor and precursor cells in vivo. Blood (in press)Google Scholar
  83. 83.
    Paquette RL, Zhou JY, Yang YC, Clark SC, Koeffler HP (1988) Recombinant gibbon interleukin-3 acts synergistically with recombinant human G-CSF and GM-CSF in vitro. Blood 71: 1569–1600Google Scholar
  84. 84.
    Park LS, Waldron PE, Friend D, Sassenfeld HM, Price V, Anderson D, Cosman D, Andrews RG, Bernstein ID, Urdal DL (1989) Interleukin-3, GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells: receptor heterogeneity and relationship to growth factor responsiveness. Blood 74: 56–65Google Scholar
  85. 85.
    Park LS, Friend D, Gillis S, Urdal DL (1986) Characterization of the cell surface receptor for a multi-lineage colony-stimulating factor (CSF-2 alpha). J Biol Chem 261: 205–210Google Scholar
  86. 86.
    Park LS, Friend D, Price V, Anderson D, Singer J, Prickett KS, Urdal DL (1989) Heterogeneity in human interleukin-3 receptors. A subclass that binds human granulocyte/macrophage colony stimulating factor. J Biol Chem 264: 5420–5427Google Scholar
  87. 87.
    Plaut M, Pierce JH, Watson CJ, Hanley-Hyde J, Nordan RP, Paul WE (1989) Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. Nature 339: 64–67Google Scholar
  88. 88.
    Quesenberry PJ, Ihle JN, McGrath E (1985) The effect of interleukin 3 and GM-CSA-2 on megakaryocyte and myeloid clonal colony formation. Blood 65: 214–217Google Scholar
  89. 89.
    Rothenburg ME, Owen WF, Silberstein DS, Woods J, Soberman RJ, Austen KF, Stevens RL (1988) Human eosinophils have prolonged survival, enhanced functional properties and became hypodense when exposed to human interleukin-3. J Clin Invest 81: 1986–1992Google Scholar
  90. 90.
    Saeland S, Caux C, Favre C, Aubry JP, Mannoni P, Pebusque MJ, Gentilhomme O, Otsuka T, Yokota T, Arai N, Arai K, Banchereau J, de Vries JE (1988) Effects of recombinant human interleukin-3 on CD34-enriched normal hematopoietic progenitors and on myeloblastic leukemia cells. Blood 72: 1580–1588Google Scholar
  91. 91.
    Saeland S, Caux C, Favre C, Duvert V, Pebusque MJ, Mannoni P, de Vries JE (1989) Combined and sequential effects of human IL-3 and GM-CSF on the proliferation of CD34+ hematopoietic cells from cord blood. Blood 73: 1195–1201Google Scholar
  92. 92.
    Saito H, Hatake K, Dvorak AM, Leiferman KM, Donnenberg AD, Arai N, Ishizaka K, Ishizaka T (1988) Selective differentiation and proliferation of hematopoietic precursor cells induced by recombinant human interleukins. Proc Natl Acad Sci USA 85: 2288–2292Google Scholar
  93. 93.
    Schleimer RP, Derse CP, Friedman B, Gillis S, Plaut M, Lichtenstein LM, MacGlashan DW Jr (1989) Regulation of human basophil mediator release by cytokines. I. Interaction with antiinflammatory steroids. J Immunol 143: 1310–1317Google Scholar
  94. 94.
    Schrader JW, Clark-Lewis I, Crapper RM, Leslie KB, Schrader S, Varigos G, Ziltener HJ (1988) The panspecific hemopoietin interleukin 3: physiology and pathology. Lymphokines 15: 281–311Google Scholar
  95. 95.
    Sieff CA, Niemeyer CM, Nathan DG, Ekern SC, Bieber FR, Yang YC, Wong G, Clark SC (1987) Stimulation of human hematopoietic colony formation by recombinant gibbon multi-colony stimulating factor or interleukin 3. J Clin Invest 80: 818–823Google Scholar
  96. 96.
    Siena S, Bregni M, Brando B, Ravagnani F, Bonadonna G, Gianni AM (1989) Circulation of CD34+ hematopoietic stem cells in the peripheral blood of high-dose cyclophosphamidetreated patients: enhancement by intravenous recombinant human granulocyte-macrophage colony-stimulating factor. Blood 74: 1905–1914Google Scholar
  97. 97.
    Sonoda Y, Yang YC, Wong GG, Clark SC, Ogawa M (1988) Erythroid burst-promoting activity of purified recombinant human GM-CSF and interleukin-3: studies with anti-GM-CSF and anti-IL-3 sera and studies in serum-free cultures. Blood 72: 1381–1386Google Scholar
  98. 98.
    Stocking C, Löliger C, Kawai M, Sucio ST, Gough N, Ostertag W (1988) Identification of genes involved in growth autonomy of hematopoietic cells by analysis of factor-independent mutants. Cell 53: 869–877Google Scholar
  99. 99.
    Tadmori W, Feingersh D, Clark SC, Choi YS (1989) Human recombinant IL-3 stimulates B cell differentiation. J Immunol 142: 1950–1955Google Scholar
  100. 100.
    Tafuri A, Lemoli RM, Gulati S, Clarkson B, Andreeff M (1989) Rationale and limitations of combined cytokine-chemotherapy treatment of acute myeloblastic leukemia (AML). Blood 74 [Suppl]: 231aGoogle Scholar
  101. 101.
    Uckun FM, Gesner TG, Song CW, Myers DE, Mufson A (1989) Leukemic B-cell precursors express functional receptors for human interleukin-3. Blood 73: 533–542Google Scholar
  102. 102.
    Umemura T, Papayannopoulou T, Stamatoyannopoulos G (1989) The mechanism of expansion of late erythroid progenitors during erythroid regeneration: Target cells and effects of erythropoietin and interleukin-3. Blood 73: 1993–1998Google Scholar
  103. 103.
    Umemura T, al-Khatti A, Donahue RE, Papayannopoulou T, Stamatoyannopoulos G (1989) Effects of interleukin-3 and erythropoietin on in vivo erythropoiesis and F-cell formation in primates. Blood 74: 1571–1576Google Scholar
  104. 104.
    Valent P, Besemer J, Muhm M, Majdic O, Lechner K, Bettelheim P (1989) Interleukin-3 activates human blood basophils via high affinity binding sites. Proc Natl Acad Sci USA 86: 5542–5546Google Scholar
  105. 105.
    Valent P, Besemer J, Maurer D, Butterfield J, Kishi K, Eckersberger F, Klepetko W, Lechner K, Bettelheim P (1990) Failure to detect interleukin-3 receptors on human mast cells. J Immunol (in press)Google Scholar
  106. 106.
    Valent P, Geissler K, Mayer P, Volc-Platzer B, Liehl E, Bettelheim P (1990) The in vivo effects of IL-3 and GM-CSF in primates. Proc I. Int Symp of Cytokines in Hemopoiesis, Oncology and Aids (in press)Google Scholar
  107. 107.
    Valent P, Geissler K, Kier P, Kalhs P, Bettelheim P (1990) Fibroblast colony stimulating activity of IL-3 and GM-CSF. Proc I. Int Symp of Cytokines in Hemopoiesis, Oncology and Aids (in press)Google Scholar
  108. 108.
    Valent P, Schmidt G, Besemer J, Mayer P, Zenke G, Liehl E, Hinterberger W, Lechner K, Maurer D, Bettelheim P (1989) Interleukin-3 is a differentiation factor for human basophils. Blood 73: 1763–1769Google Scholar
  109. 109.
    Vellenga E, Ostapovicz, O'Rourke B, Griffin JD (1987) Effects of recombinant IL-3, GM-CSF, and G-CSF on proliferation of leukemic clonogenic cells in short-term and longterm cultures. Leukemia 1: 584–589Google Scholar
  110. 110.
    Volc-Platzer B, Valent P, Radaszkiewicz T, Mayer P, Bettelheim P, Wolff K (1990) Recombinant human Interleukin-3 induces proliferation of keratinocytes and allergic effector cells in non human primates (submitted)Google Scholar
  111. 111.
    Whetton AD, Dexter TM (1988) The mode of action of interleukin 3 in promoting survival, proliferation, and differentiation of hemopoietic progenitor cells. Lymphokines 15: 355–373Google Scholar
  112. 112.
    Whetton AD, Monk PN, Consalvey SD, Huang SJ, Dexter TM, Downes CP (1988) Interleukin 3 stimulates proliferation via protein kinase C activation without increasing inositol lipid turnover. Proc Natl Acad Sci USA 85: 3284–3288Google Scholar
  113. 113.
    Wodnar-Filipowicz A, Heusser CH, Moroni C (1989) Production of the haemopoietic growth factors GM-CSF and interleukin-3 by mast cells in response to IgE receptor-mediated activation. Nature 339: 150–152Google Scholar
  114. 114.
    Woermann B, Gesner TG, Mufson RA, LeBien TW (1989) Proliferative effect of interleukin-3 on normal and leukemic human B cell precursors. Leukemia 3: 399–404Google Scholar
  115. 115.
    Wong PM, Chung SW, Dunbar CE, Bodine DM, Ruscetti S, Nienhuis AW (1989) Retrovirus-mediated transfer and expression of the interleukin-3 gene in mouse hematopoietic cells result in a myeloproliferative disorder. Mol Cell Biol 9: 798–808Google Scholar
  116. 116.
    Yang YC, Ciarletta AB, Temple PA, Chung MP, Kovacic S, Witek-Gianotti JS, Leary AC, Kriz R, Donahue RE, Wong GG, Clark SC (1986) Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell 47: 3–10Google Scholar
  117. 117.
    Yang YC, Kovacic S, Kriz R, Wolf S, Clark SC, Wellems TE, Nienhuis A, Epstein N (1988) The human genes for GM-CSF and IL 3 are closely linked in tandem on chromosome 5. Blood 71: 958–961Google Scholar
  118. 118.
    Yang YC, Clark SC (1989) Interleukin-3: molecular biology and biologic activities. Hematol/Oncol Clin North Am 3: 441–452Google Scholar
  119. 119.
    Zhou YQ, Stanley ER, Clark SC, Hatzfeld JA, Levesque JP, Federici C, Watt SM, Hatzfeld A (1988) Interleukin-3 and interleukin-1 alpha allow earlier bone marrow progenitors to respond to human colony-stimulating factor 1. Blood 72: 1870–1874Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Peter Valent
    • 1
  • Klaus Geissler
    • 1
  • Christian Sillaber
    • 1
  • Klaus Lechner
    • 1
  • Peter Bettelheim
    • 1
  1. 1.I. Medical Department, Division of HematologyUniversity of ViennaViennaAustria

Personalised recommendations