|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.