|Budget Amount *help
¥6,000,000 (Direct Cost : ¥6,000,000)
Fiscal Year 1991 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1990 : ¥4,000,000 (Direct Cost : ¥4,000,000)
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.
以上のようにin vitro,in vivoの巨核球・血小板造血はいくつかのサイトカインにより修飾を受けることが示されたが,中でもILー6の血小板増加作用は検系したサイトカイン中最もpotentであり,マウスにおける長期投与実験およびprimateにおける実験でも副作用は軽徴でありまた可逆的であったことから、今後,血小板増加因子として臨床的応用への可能性が追求されうるものと考える。