The study on thrombopoietic activity of interleukin 6

白细胞介素6血小板生成活性的研究

• 批准号: 02454520
• 负责人: KIMURA Hideo
• 金额: $ 3.84万
• 依托单位: Fukushima Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454520/
• 关键词: Interleukin 6; cytokines; megakaryocytopoiesis; thrombocytopoiesis; thrombopoietin; 血小板産産; Interleukinー6; 血小板造血; 巨核球; Thrombopoietic factor

We have initially shown that several cytokines modulate in vitro megakaryocytopoiesis, either as Meg-CSF (early factor) or as megakaryocyte maturation factor (late factor). Interleukin-3 (IL-3), erythropoietin (Epo), and granulocytemacrophage colony-stimulating factor (GM-CSF) stimulated megakaryocyte colony growth ; IL-3, GM-CSF, Epo, macrophage (M)-CSF and IL-6 promoted maturation of megakaryocytes in liquid culture system whereas granulocyte (G)-CSF and IL-lb did not have a stimulatory effect on megakaryocytopoiesis in vitro. To determine if some of these cytokines stimulate thrombocytopoiesis in vivo, in vivo administrations (i. p., 5 days) of each cytokine were performed in mouse. Although GM-CSF, G-CSF and M-CSF did not influence on platelet count, IL6 and IL-lb induced a marked increase in platelet levels associated with an increment in marrow megakaryocyte size. Epo elicited a mild, but transient increase in platelet counts. The effect of IL-6 on megakaryocytopoiesis and thrombocytopoiesis was considered direct, because IL-6 receptors were demonstrated on megakaryocytes (using highly purified rat megakaryocytes). As IL-lb had no effects on megakaryocytopoiesis in vitro, the in vivo effect of IL-lb on thrombocytopoiesis was possibly mediated via IL-6 by determinations of serum levels for several cytokines in the mice injected with IL-lb. The long-term administration of IL-6 to mice revealed that the effect persists as long as IL-6 are administrated. The stimulatory effect of IL-6 was also confirmed in primates. Since side effects of this cytokine were minimum and reversible in mice and primates in the doses studied, IL-6 is probably useful as a thrombopoiesis-stimulatory factor in patients with thrombocytopenia.

我们已经初步表明，几种细胞因子调节体外巨核细胞生成，无论是巨核细胞集落刺激因子（早期因子）或巨核细胞成熟因子（晚期因子）。白细胞介素-3（IL-3）、促红细胞生成素（Epo）、粒细胞巨噬细胞集落刺激因子（GM-CSF）对巨核细胞集落生长有促进作用，而粒细胞（G）-CSF、IL-1b对巨核细胞集落生成无促进作用。为了确定这些细胞因子中的一些是否在体内刺激血小板生成，体内给药（i. p.的情况下，5天）。尽管GM-CSF、G-CSF和M-CSF不影响血小板计数，但IL-6和IL-1b诱导与骨髓巨核细胞大小增加相关的血小板水平的显著增加。促红细胞生成素引起血小板计数轻度但短暂的增加。IL-6对巨核细胞生成和血小板生成的作用被认为是直接的，因为在巨核细胞上证明了IL-6受体（使用高度纯化的大鼠巨核细胞）。由于IL-1b在体外对巨核细胞生成没有影响，因此IL-1b对血小板生成的体内影响可能通过测定注射IL-1b的小鼠中几种细胞因子的血清水平而经由IL-6介导。对小鼠长期施用IL-6显示，只要施用IL-6，效果就持续。在灵长类动物中也证实了IL-6的刺激作用。由于这种细胞因子的副作用是最小的和可逆的，在小鼠和灵长类动物的剂量研究，IL-6可能是有用的血小板减少症患者的血小板生成刺激因子。

项目成果

Shikama Y et al.: "Transient effect of erythropoietin on thrombocytopoiesis in vivo in mice." Exp Hematol. 20. 216-222 (1992)

Shikama Y 等人：“促红细胞生成素对小鼠体内血小板生成的短暂影响。”

Kimura H,Ishibashi T et al.: "Interleukin 6 is a differentiation factor for human megakaryocytes in vitro" Eur J Immunol. 20. 1927-1931 (1990)

Kimura H、Ishibashi T 等人：“白细胞介素 6 是体外人类巨核细胞的分化因子”Eur J Nutrition。

Kimura H, Ishibashi T, et al.: "Interleukin 6 is a differentiation factor for human megakaryocytes in vitro." Eur J Immunol. 20. 1927-1931 (1990)

Kimura H、Ishibashi T 等人：“白细胞介素 6 是体外人类巨核细胞的分化因子。”

Kimura H,Ishibashi T et al.: "Interleukin 6 is a differentiation factor for human megakaryocytes in vitro" Eur.J.Immunol.20. 1927-1931 (1990)

Kimura H、Ishibashi T 等人：“白细胞介素 6 是体外人类巨核细胞的分化因子”Eur.J.Immunol.20。

Shikama Y.Ishibashi.T,Kimura H.et al.: "Expression of ILー6 receptors on purified rat megakaryocytes using an immuno magnetic procedure" Blood(abstract,full paper). 76. 475a (1990)

Shikama Y.Ishibashi.T、Kimura H.等人：“使用免疫磁性程序在纯化的大鼠巨核细胞上表达 IL-6 受体”血液（摘要，全文）76. 475a (1990)。