重组IL－6与IL－3或／和GM－CSF合用对正常BN大鼠粒单系体外造血的调控效应

本研究探讨了重组人ＩＬ－６与大鼠ＩＬ－３和／或小鼠ＧＭ－ＣＳＦ结合对正常ＢＮ大鼠粒单系体外造血的调控效应。结果表明，ＩＬ－６在１０００－４０００Ｕ／ｍｌ呈剂量依赖性刺激粒系造血祖细胞集落形成及骨髓细胞的ＤＮＡ合成，集落以ＧＭ型为主，其刺激活性低于ＩＬ－３或ＣＭ－ＣＳＦ。ｌＬ－６与ＩＬ－３和／或ＧＭ－ＣＳＦ的结合对粒单系集落形成及ＤＮＡ合成无协同或相加作用，甚至出现拮抗效应，但却显著增大集落。提示ＩＬ－６可能具有双向调控作用，促进早期造血细胞的增殖，拮抗其它因子对晚期粒单系造血的刺激作用；具有重叠生物效应的这３种细胞因子在调控造血时，它们之间的相互作用应是顺序的而不是同时的。

COMBINED EFFECTS OF INTERLEUKIN-6 WITH INTERLEUKIN-3OR GRANULOCYTE-MACROPHAGE COLONYSTIMULATING FACTOR ON GRANULOPOIESIS OF BN RAT BONE MARROWIN VITRO

In the present study,IL-6 was assessed for its regulating effects on granulopoiesis of bonemarrow cells of BN rat in the presence or absence of lL-3 and GM-CSF. IL-6 by itself,at dosesof lU /L to 4U/L,was able to stimulate moderately granulocyte-macrophage colony-formingunits(CFU-GM )and DNA synthesis of unpurified nomal bone marrow. The optimal stimu-lating concentration of IL-6 approxmated 4U/L, whereas a weaker stimulation was observed athigher concentration of 5U/L as compared with that induced by 4U/L. No synergistic oradditive effect on colony formation and DNA synthesis were observed when IL-6 at higher con-centration was combined with IL-3, GM-CSF or IL-3 GM-CSF at optimal dose. In contrast,IL-6 showed antagonistic effect on CFU-GM stimulated by IL-3 and no influence on that in-duced by GM-CSF. In3 H-TdR incorporation assay, the antagonistic effect of IL-6 on DNAsynthesis in bone marrow cells stimulated by IL-3 or GM-CSF was far more obvious. Similarantagonistic actions were also observed with the combinations of IL-3 GM-CSF andIL-6 IL-3 GM-CSF. All of these factor combinations induced colonies larger than those in-duced by individual factor.Thus,these results provide further evidence that IL-6 might have adual actions on normal hematopoiesis:enhancement of proliferation of primitive hematopoieticcells in early stage of maturation and antagonism in the later stage of granulopoiesis stimulatedby other factors.These findings are in agreement with schemes of hematopoiesis in which theinteractions between certain cytokines sharing the overlapping properties in a developmentalpathway of lineage-restrictive progenitor cells should be sequential rather than simultaneous.