|
|
 Previous Article | Table of Contents | Next Article 
Recombinant glycosylated human interleukin-6 accelerates peripheral blood
platelet count recovery in radiation-induced bone marrow depression in
baboons
F Herodin, JC Mestries, D Janodet, S Martin, J Mathieu, MP Gascon, MO Pernin and A Ythier
Department of Radiobiology, Centre de Recherches du Service de Sante des
Armees, La Tronche, France.
This report was aimed at confirming the potential clinical use for a
genetically engineered glycosylated human interleukin-6 (rhIL-6) in
hematopoiesis. Its tolerance and efficacy were assessed on hematopoietic
restoration after neutron radiation-induced bone marrow injury on baboons,
which represent an adequate model of parallelism for studying hematology in
the human. The particular neutron radiation absorption pattern in the body
allows the preservation of underexposed bone marrow areas that mimics an
autotransplantation-like situation. An initial dose finding study (1
microgram up to 20 micrograms/kg/d for 8 consecutive days) in normal
baboons established a dose-dependent response regarding the peripheral
platelet count (range of increase, 1.5- to 4-fold). A significant elevation
in white blood cell (WBC) count, as well as a substantial reversible
normochromic normocytic anemia, were observed for the highest doses only
(10 and 20 micrograms/kg/d). All rhIL-6 administered doses were clinically
well tolerated. In myelosuppressed baboons, a selected dose of 10
micrograms/kg/d of rhIL-6 for 13 consecutive days significantly lessened
the degree of induced thrombocytopenia as compared with the control group
(P = .01) and shortened the time to occurrence of the nadir, showing that
the onset of recovery occurs much earlier, ie, an average of 5 days (P =
.003), in the treated group. Moreover, this accelerated platelet recovery
is evidenced by an 8-day shorter mean time back to baseline values (P =
.03) in the rhIL-6--treated animals. At this dose no effect was observed on
the WBC recovery pattern. Importantly rhIL-6 did not accentuate the
radiation-induced anemia and was clinically well tolerated. All tested
monkeys recovered from their induced pancytopenia and no animal loss was
recorded. IL-6, tumor necrosis factor, and IL-1 blood measurements are
reported. In conclusion, rhIL-6 is a potent thrombopoietic factor for the
treatment of induced thrombocytopenia in nonhuman primates at a clinically
well- tolerated dose.
Volume 80,
Issue 3,
pp. 688-695,
08/01/1992
Copyright © 1992 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. L. Angiolillo, V. Davenport, M. A. Bonilla, C. van de Ven, J. Ayello, O. Militano, L. L. Miller, M. Krailo, G. Reaman, and M. S. Cairo
A Phase I Clinical, Pharmacologic, and Biologic Study of Thrombopoietin and Granulocyte Colony-Stimulating Factor in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Recurrent or Refractory Solid Tumors: A Children's Oncology Group Experience
Clin. Cancer Res.,
April 1, 2005;
11(7):
2644 - 2650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Drouet, F. Mourcin, N. Grenier, V. Leroux, J. Denis, J.-F. Mayol, P. Thullier, J.-J. Lataillade, and F. Herodin
Single administration of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and interleukin-3 in combination soon after irradiation prevents nonhuman primates from myelosuppression: long-term follow-up of hematopoiesis
Blood,
February 1, 2004;
103(3):
878 - 885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Bracho, M. D. Krailo, V. Shen, S. Bergeron, V. Davenport, W. Liu-Mares, B. R. Blazar, A. Panoskaltsis-Mortari, C. van de Ven, R. Secola, et al.
A Phase I Clinical, Pharmacological, and Biological Trial of Interleukin 6 Plus Granulocyte-Colony Stimulating Factor after Ifosfamide, Carboplatin, and Etoposide in Children with Recurrent/Refractory Solid Tumors: Enhanced Hematological Responses but a High Incidence of Grade III/IV Constitutional Toxicities
Clin. Cancer Res.,
January 1, 2001;
7(1):
58 - 67.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Drouet, J. Mathieu, N. Grenier, E. Multon, J.-J. Sotto, and F. Herodin
The Reduction of In Vitro Radiation-Induced Fas-Related Apoptosis in CD34+ Progenitor Cells by SCF, FLT-3 Ligand, TPO, and IL-3 in Combination Resulted in CD34+ Cell Proliferation and Differentiation
Stem Cells,
September 1, 1999;
17(5):
273 - 285.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. Andrews, A Winkler, D Myerson, R. Briddell, G. Knitter, I. McNiece, and P Hunt
Recombinant human ligand for MPL, megakaryocyte growth and development factor (MGDF), stimulates thrombopoiesis in vivo in normal and myelosuppressed baboons
Stem Cells,
November 1, 1996;
14(6):
661 - 677.
[Abstract]
|
|
|
|
|
