Carrington P A, Hill R J, Stenberg P E, Levin J, Corash L, Schreurs J, Baker G, Levin F C
Department of Laboratory Medicine, University of California School of Medicine, San Francisco.
Blood. 1991 Jan 1;77(1):34-41.
The in vivo effects of interleukin-3 (IL-3), interleukin-6 (IL-6), and a combination of IL-3 plus IL-6 on murine megakaryocytopoiesis and thrombopoiesis were examined. Human recombinant IL-6 was administered subcutaneously as 14 equal injections of 5,000 units each during a 102-hour period. Murine recombinant IL-3 was given as 8 injections of 80,000 units each during the first 54 hours. Megakaryopoiesis and thrombopoiesis were evaluated 120 hours after initial administration of the cytokines. Platelet levels increased by 20% following IL-3 alone, 35% following IL-6 alone and 61% after administration of both IL-3 and IL-6. Platelet production, as measured by 75Se-selenomethionine incorporation, increased by approximately 120% in animals that had received IL-6 or IL-3 plus IL-6. Megakaryocyte ploidy analysis by two-color flow cytometry showed a shift in the modal ploidy class from 16N to 32N and a significant increase in the frequency of 64N cells only in IL-6 treated animals. Both bone marrow and splenic megakaryocyte colony-forming cells were significantly increased following either IL-3 or IL-6. Bone marrow megakaryocyte size increased 18%, 43%, and 38%, respectively, after administration of IL-3, IL-6, or the combination of IL-3 plus IL-6. Leukocyte counts and hematocrits were unaffected by either cytokine. Additional groups of mice received the same injection schedule as above and the serial effects on peripheral blood cell levels were assessed for 30 days. Platelet levels, which had been elevated by IL-3 or IL-6, fell to control values within 4 days following the last injection. Animals given IL-6 or IL-3 plus IL-6 were subsequently thrombocytopenic relative to controls on days 7 through 9 following cessation of treatment. Temporary 'cycling' of platelet levels was observed for 3 weeks following treatment with IL-6 or the combination of IL-3 plus IL-6. We conclude that IL-6 and to a lesser extent IL-3 stimulate platelet production in vivo and that their combined effects on platelet levels are approximately additive. Following discontinuation of IL-3 or IL-6, the effects are rapidly reversed, presumably by negative feedback mechanisms, resulting in a period of 'rebound thrombocytopenia' in mice that had received IL-6.
研究了白细胞介素-3（IL-3）、白细胞介素-6（IL-6）以及IL-3与IL-6联合使用对小鼠巨核细胞生成和血小板生成的体内作用。人重组IL-6在102小时内皮下注射14次，每次5000单位。小鼠重组IL-3在最初的54小时内分8次注射，每次80000单位。在首次给予细胞因子120小时后评估巨核细胞生成和血小板生成。单独使用IL-3后血小板水平增加20%，单独使用IL-6后增加35%，而同时给予IL-3和IL-6后增加61%。通过75Se-硒蛋氨酸掺入法测定，接受IL-6或IL-3加IL-6的动物血小板生成增加约120%。通过双色流式细胞术进行的巨核细胞倍性分析显示，仅在接受IL-6治疗的动物中，模态倍性类别从16N转变为32N，且64N细胞的频率显著增加。给予IL-3或IL-6后，骨髓和脾脏中的巨核细胞集落形成细胞均显著增加。给予IL-3、IL-6或IL-3加IL-6后，骨髓巨核细胞大小分别增加18%、43%和38%。两种细胞因子均未影响白细胞计数和血细胞比容。另外几组小鼠接受与上述相同的注射方案，并评估对外周血细胞水平的连续影响，为期30天。由IL-3或IL-至6升高的血小板水平在最后一次注射后4天内降至对照值。在停止治疗后的第7至9天，接受IL-6或IL-3加IL-6的动物相对于对照组出现血小板减少。在用IL-6或IL-3加IL-6治疗后3周内观察到血小板水平的暂时“循环”。我们得出结论，IL-6以及在较小程度上IL-3可在体内刺激血小板生成，并且它们对血小板水平的联合作用大致是相加的。停用IL-3或IL-6后，其作用迅速逆转，推测是通过负反馈机制，导致接受过IL-6的小鼠出现一段“反弹性血小板减少”期。
