Recombinant human interleukin-11 stimulates megakaryocytopoiesis and increases peripheral platelets in normal and splenectomized mice

Neben, TY; Loebelenz, J; Hayes, L; McCarthy, K; Stoudemire, J; Schaub, R; Goldman, SJ

doi:10.1182/blood.v81.4.901.bloodjournal814901

Cited by 16 publications

(31 citation statements)

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“…Schaub, unpublished observation). Splenectomy did not alter the ability of rHuIL-11 to stimulate megakaryocytopoiesis and to increase peripheral platelets in mice [19].…”

Section: Peripheral Hematology and Platelet Responsesmentioning

confidence: 79%

“…In mice, rHuIL-1 1 (150 pgkglday) administered S.C. for seven days produced a 30-50% increase in peripheral platelet counts peaking on day 7 and remaining elevated on day 10. Continued administration of rHuIL-11 for 14 days at the same dose produced increases in peripheral platelets of the same magnitude; however, the platelet count remained elevated until day 17 [19]. A dose response study of 7-day S.C. administration of rHuIL-11 showed a significant increase in platelet counts at 36 pgkglday with optimal stimulation of platelets at 250 pg/kg/day [21].…”

Section: Peripheral Hematology and Platelet Responsesmentioning

confidence: 92%

“…Initial studies indicated that stimulation of peripheral platelets was the major in vivo activity of rHuIL-I1 in naive mice and rats [3,19,201. In mice, rHuIL-1 1 (150 pgkglday) administered S.C. for seven days produced a 30-50% increase in peripheral platelet counts peaking on day 7 and remaining elevated on day 10.…”

Section: Peripheral Hematology and Platelet Responsesmentioning

confidence: 99%

“…Delivery of rHuIL-11 to mice by continuous S.C. infusion enhanced biological response, increasing peripheral platelet counts by 150%, compared to 45-50% in mice treated by S.C. injection [22, 231. In both mice and rats, increases in peripheral platelets were accompanied by a shift to higher ploidy megakaryocytes (32N) in the bone marrow and increased megakaryocyte size with the most dramatic shifts occurring in mice treated by constant s .~. infusion [19,20,22,231. There was no significant change in the total number of bone marrow megakaryocytes; however, there was a three-fold increase in histologically identifiable megakaryocytes in the spleens of normal mice after treatment with rHuIL-11 for seven days ( R .…”

Section: Peripheral Hematology and Platelet Responsesmentioning

confidence: 99%

“…rHuIL-1 1 has been tested in several murine models of chemotherapy and/or irradiationinduced myelosuppression, as well as in models of bone marrow transplant following myeloablation [19,21,29,[32][33][34]. Although administration of rHuIL-11 as a single agent to normal animals primarily stimulated megakaryocytopoiesis and thrombopoiesis, treatment of myelosuppressed animals with rHuIL-11 resulted in multilineage hematopoietic stimulation in most models.…”

Section: Rhuil-11 Administration To Myelosuppressed Animalsmentioning

confidence: 99%

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Preclinical biology of interleukin 11: A multifunctional hematopoietic cytokine with potent thrombopoietic activity

Goldman¹

1995

STEM CELLS

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Interleukin 11 (IL-11) is a multifunctional hematopoietic cytokine which was originally identified as a factor produced by an IL-1-stimulated primate stromal cell line. The in vitro biological activities of recombinant human (rHu)IL-11 result predominantly from synergistic interactions with other growth factors. In combination with other cytokines, rHuIL-11 has been shown to support the formation of primitive hematopoietic and lymphohematopoietic progenitor colonies from bone marrow, to promote erythroid burst formation and to stimulate both early and late stages of megakaryocyte proliferation and differentiation. rHuIL-11 is biologically active in mice, rats, dogs and primates when administered as a single agent in vivo. The predominant effect of rHuIL-11 in naive mice was on cells of the megakaryocytic lineage, increasing the number of bone marrow megakaryocyte progenitors, stimulating megakaryocyte endoreplication and increasing peripheral platelet counts in a dose-dependent fashion. Similar megakaryocytic stimulatory activity was seen in nonhuman primates treated with rHuIL-11 where platelet counts were increased by as much as 300%. In several models of severe myelosuppression induced by chemotherapy and/or irradiation and in bone marrow transplant models, there were multilineage hematopoietic stimulation following rHuIL-11 treatment. In these models, accelerated recovery of platelets was a consistent observation, while some models show enhanced neutrophil and red blood cell recovery as well. These results from preclinical studies confirm the broad spectrum of biological activities exhibited by rHuIL-11 in vitro, and suggest that this cytokine may be an effective agent in the treatment of myelosuppression and thrombocytopenia associated with cancer chemotherapy and bone marrow transplantation.

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“…Schaub, unpublished observation). Splenectomy did not alter the ability of rHuIL-11 to stimulate megakaryocytopoiesis and to increase peripheral platelets in mice [19].…”

Section: Peripheral Hematology and Platelet Responsesmentioning

confidence: 79%

Section: Peripheral Hematology and Platelet Responsesmentioning

confidence: 92%

Section: Peripheral Hematology and Platelet Responsesmentioning

confidence: 99%

Section: Peripheral Hematology and Platelet Responsesmentioning

confidence: 99%

Section: Rhuil-11 Administration To Myelosuppressed Animalsmentioning

confidence: 99%

See 3 more Smart Citations

Preclinical biology of interleukin 11: A multifunctional hematopoietic cytokine with potent thrombopoietic activity

Goldman¹

1995

STEM CELLS

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Thrombopoietic Activity of Recombinant Human Interleukin 11 (rHuIL‐11) in Normal and Myelosuppressed Nonhuman Primates

Schlerman¹,

Bree²,

Kaviani³

et al. 1996

STEM CELLS

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Abstract. We have extensively characterized the hematological response of normal and myelosuppressed nonhuman primates to treatment with recombinant human interleukin 11 (rHuIL-11) in vivo. In normal cynomolgus monkeys, rHuIL-11 significantly increased peripheral platelet counts when administered at doses of 10 µg/kg/day to 100 µg/kg/day either by constant i.v. infusion or s.c. injection. As few as four days of rHuIL-11 treatment were sufficient to increase peripheral platelet counts significantly. In addition, extending the treatment period enhanced both the magnitude and the duration of the response. Bone marrow megakaryocytes from animals treated with 100 µg/kg/day of rHuIL-11 were increased in size compared to controls and were ultrastructurally normal. A nonhuman primate myelosuppression model using carboplatin, which causes severe thrombocytopenia with platelet counts of ≤20 × 10 3 platelets/µl, was developed. This novel model was used to evaluate the effectiveness of rHuIL-11 in platelet restoration. rHuIL-11, administered s.c. at a dose of 125 µg/kg/day either concurrently or following chemotherapy, prevented severe thrombocytopenia in addition to accelerating platelet recovery compared to control animals receiving no rHuIL-11. These data demonstrate that rHuIL-11 has potent in vivo thrombopoietic effects when administered to normal and myelosuppressed nonhuman primates, and that rHuIL-11 can be an important therapy to reduce the severity and duration of thrombocytopenia following chemotherapy.

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Serum Thrombopoietin Level in Various Hematological Diseases

et al. 1996

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Abstract. To investigate the pathophysiological role of thrombopoietin (TPO) in thrombopoiesis, we measured its serum levels in 15 healthy individuals, 84 patients with various hematological diseases and 2 patients with liver cirrhosis using an enzyme immunoassay procedure. The TPO level was 0.84 ± 0.40 f mol/ml in normal individuals. TPO levels were considerably elevated in patients with myelosuppression after intensification chemotherapy of acute leukemia in complete remission (postchemotherapy group; n = 18; 18.46 ± 9.70 f mol/ml). When the data of normal individuals and the postchemotherapy group were combined, TPO levels were inversely correlated with the platelet count in this combined group. We compared these data of normal individuals and the postchemotherapy group with various hematological disease states. In aplastic anemia (n = 13; 16.03 ± 9.44 f mol/ml), acute lymphoblastic leukemia (n = 5; 10.36 ± 5.57 f mol/ml), malignant lymphoma (n = 6; 2.79 ± 2.27 f mol/ml), multiple myeloma (n = 3; 3.34 ± 0.20 f mol/ml) and chronic lymphocytic leukemia (n = 2; 1.71 ± 3.91 f mol/ml), the relationship of serum TPO levels and platelet counts was almost the same as in the combined group with normal individuals and the postchemotherapy group. However, the TPO levels were slightly higher in myeloproliferative disorders (n = 12; 1.99 ± 1.47 f mol/ml) and lower in acute myelogenous leukemia (n = 8; 2.27 ± 1.25 f mol/ml), hypoplastic leukemia (n = 3; 2.76 ± 2.23 f mol/ml), myelodysplastic syndrome (n = 2; 0.42 ± 0.60 f mol/ml), liver cirrhosis (n = 2; 1.50 ± 0.92 f mol/ml) and idiopathic thrombocytopenic purpura (n = 12; 2.08 ± 1.41 f mol/ml), when compared to the regression line for the combined group with normal individuals and postchemotherapy group. These findings suggest that TPO might play an important role in regulation of the platelet count in normal and pathological conditions.

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Recombinant human interleukin-11 stimulates megakaryocytopoiesis and increases peripheral platelets in normal and splenectomized mice

Cited by 16 publications

References 0 publications

Preclinical biology of interleukin 11: A multifunctional hematopoietic cytokine with potent thrombopoietic activity

Preclinical biology of interleukin 11: A multifunctional hematopoietic cytokine with potent thrombopoietic activity

Thrombopoietic Activity of Recombinant Human Interleukin 11 (rHuIL‐11) in Normal and Myelosuppressed Nonhuman Primates

Serum Thrombopoietin Level in Various Hematological Diseases

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