Chang M, Suen Y, Meng G, Buzby J S, Bussel J, Shen V, van de Ven C, Cairo M S
Division of Hematology/Oncology and Blood and Marrow Transplantation, Children's Hospital of Orange Country, CA 92668, USA.
Blood. 1996 Nov 1;88(9):3354-62.
The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. To determine the relationship of endogenous thrombopoietic cytokine levels and circulating platelet (PLT) counts, we measured the levels of thrombo-poietin (TPO), interleukin-11 (IL-11), and interleukin-6 (IL-6) in patients with significant thrombocytopenia secondary to both marrow hypoplasia and increased PLT destruction. Increased endogenous levels of TPO and IL-11, but not IL-6, were detected in bone marrow transplant patients with thrombocytopenia following myeloablative therapy (BMT/MAT) (TPO: 1,455.5 +/- 87.3 pg/mL, [PLT 39,600 +/- 7,800/microL], P < .001, n = 12; IL-11: 227.9 +/- 35 pg/mL, [PLT 32,900 +/- 57,000/microL], P < .05, n = 19; IL-6: 25.8 +/- 8.4 pg/mL, [PLT 32,800 +/- 5,057/microL], P > .05, n = 4] v normal donors [TPO < 150 pg/mL, n = 8; IL-11 < 50 pg/mL, n = 9; IL-6 < 10 pg/mL, n = 5 [PLT 203,000 +/- 7,500/microL]. There was a significant inverse correlation between endogenous levels of TPO and IL-11, but not IL-6, and PLT counts in the MAT/BMT patients (TPO: r = -0.57, P < .0001, n = 188; IL-11: r = -0.329, P < .0001, n = 249; IL-6: r = -0.1147, P > .05, n = 62). In patients with immune thrombocytopenia purpura (ITP), with decreased PLT survival, but intact bone marrow megakaryocytopoiesis, endogenous IL-11 levels were significantly increased (328.0 +/- 92.6 pg/mL, [PLT: 20,900 +/- 3,000/microL], P < .05, n = 25). However, endogenous TPO levels remained undetectable (< 150 pg/mL, [PLT 30,500 +/- 5,500/microL], n = 15). These results suggest that there may be differential mechanisms regulating endogenous TPO, IL-11, and IL-6 levels during acute thrombocytopenia and suggest that the absolute number of circulating PLTs may not always be the sole regulator of endogenous TPO levels. Other mpl-expressing cells of the megakaryocyte lineage may contribute to the regulation of circulating TPO levels as well. Our results also suggest IL-11 levels may in part, be regulated by a negative feedback loop based on circulating PLT counts, but also may, in part, be regulated by a variety of inflammatory agonists. Both TPO and IL-11, therefore, appear to be active thrombopoietic cytokines regulating, in part, megakaryocytopoiesis during states of acute thrombocytopenia.
巨核细胞生成和血小板生成的调节似乎受一系列造血生长因子的控制。为了确定内源性血小板生成细胞因子水平与循环血小板（PLT）计数之间的关系，我们检测了继发于骨髓发育不全和PLT破坏增加的严重血小板减少症患者的血小板生成素（TPO）、白细胞介素-11（IL-11）和白细胞介素-6（IL-6）水平。在接受清髓性治疗后出现血小板减少的骨髓移植患者（BMT/MAT）中，检测到内源性TPO和IL-11水平升高，但IL-6未升高（TPO：1455.5±87.3 pg/mL，[PLT 39600±7800/μL]，P<.001，n = 12；IL-11：227.9±35 pg/mL，[PLT 32900±57000/μL]，P<.05，n = 19；IL-6：25.8±8.4 pg/mL，[PLT 32800±5057/μL]，P>.05，n = 4），而正常供者中TPO<150 pg/mL，n = 8；IL-11<50 pg/mL，n = 9；IL-6<10 pg/mL，n = 5[PLT 203000±7500/μL]。在MAT/BMT患者中，内源性TPO和IL-11水平与PLT计数之间存在显著负相关，但IL-6与PLT计数之间无显著负相关（TPO：r = -0.57，P<.0001，n = 188；IL-11：r = -0.329，P<.0001，n = 249；IL-6：r = -0.1147，P>.05，n = 62）。在血小板生存时间缩短但骨髓巨核细胞生成正常的免疫性血小板减少性紫癜（ITP）患者中，内源性IL-11水平显著升高（328.0±92.6 pg/mL，[PLT：20900±3000/μL]，P<.05，n = 25）。然而，内源性TPO水平仍检测不到（<150 pg/mL，[PLT 30500±5500/μL]，n = 15）。这些结果表明，在急性血小板减少症期间，调节内源性TPO、IL-11和IL-6水平的机制可能存在差异，提示循环PLT的绝对数量可能并不总是内源性TPO水平的唯一调节因子。巨核细胞系中其他表达mpl的细胞也可能参与循环TPO水平的调节。我们的结果还表明，IL-11水平可能部分受基于循环PLT计数的负反馈回路调节，但也可能部分受多种炎性激动剂调节。因此，TPO和IL-11似乎都是活跃的血小板生成细胞因子，在急性血小板减少症状态下部分调节巨核细胞生成。
