Wang C Q, Udupa K B, Lipschitz D A
Geriatric Research, Education and Clinical Center (GRECC), John L. McClellan Memorial Veterans Hospital, Little Rock, Arkansas 72205, USA.
J Cell Physiol. 1996 Feb;166(2):305-10. doi: 10.1002/(SICI)1097-4652(199602)166:2<305::AID-JCP8>3.0.CO;2-T.
Interleukin-10 (IL-10) has been shown to exert anti-inflammatory effects by suppressing macrophage proliferation and inhibiting cytokine production. In this study we show that in the presence of erythropoietin (EPO), the addition of IL-10 results in a significant dose-dependent increase in both Burst Forming Unit-Erythroid (BFU-E) and Colony Forming Unit-Erythroid (CFU-E) colony growth in both serum-containing and serum-free murine cultures in vitro. IL-10 acts at the later stages of erythroid cell proliferation and differentiation as the increase in colony number was greater in CFU-E than in BFU-E, and was similar when IL-10 was added to BFU-E cultures at the time of culture initiation as when its addition to culture was delayed for 7 days. Furthermore, no increase in BFU-E colony number was noted when IL-10, added at the time of culture initiation, was neutralized by the addition to culture of a monoclonal anti-IL-10 antibody up to 7 days later. The increases in BFU-E by IL-10 addition were not the result of prolongation of BFU-E colony lifespan, which was not significantly different in IL-10 treated and control cultures, respectively. Rather IL-10 stimulated the proliferation of erythroid clusters that were now large enough to be recognized as colonies. IL-10-induced stimulation of erythropoiesis appeared to be independent of its inhibitory effects on macrophage function, as stimulation of erythroid colony growth was similar in macrophage-containing and depleted cultures. Studies to determine if the IL-10 effect was direct or indirect yielded equivocal results. A limiting dilution assay suggested a direct effect. However, a log/log dose response curve with IL-10 did not pass through the origin suggesting an indirect effect. These studies indicate that IL-10 acts synergistically with EPO to significantly increase stimulation of erythroid differentiation and proliferation in vitro and may be involved in the regulation of normal erythropoiesis in vivo.
白细胞介素-10（IL-10）已被证明可通过抑制巨噬细胞增殖和抑制细胞因子产生来发挥抗炎作用。在本研究中，我们发现，在存在促红细胞生成素（EPO）的情况下，添加IL-10会导致体外含血清和无血清的小鼠培养物中爆式红系集落形成单位（BFU-E）和红系集落形成单位（CFU-E）集落生长均出现显著的剂量依赖性增加。IL-10作用于红系细胞增殖和分化的后期阶段，因为CFU-E中集落数量的增加大于BFU-E，并且在培养开始时将IL-10添加到BFU-E培养物中与将其添加延迟7天时相似。此外，在培养开始时添加的IL-10在长达7天后通过向培养物中添加单克隆抗IL-10抗体进行中和时，未观察到BFU-E集落数量增加。添加IL-10导致的BFU-E增加并非BFU-E集落寿命延长的结果，在IL-10处理的培养物和对照培养物中，BFU-E集落寿命分别无显著差异。相反，IL-10刺激了红系细胞簇的增殖，这些细胞簇现在足够大，可以被识别为集落。IL-10诱导的红细胞生成刺激似乎与其对巨噬细胞功能的抑制作用无关，因为在含巨噬细胞和不含巨噬细胞的培养物中，红系集落生长的刺激相似。关于确定IL-10的作用是直接还是间接的研究产生了不确定的结果。有限稀释分析表明有直接作用。然而，IL-10的对数/对数剂量反应曲线未通过原点，表明有间接作用。这些研究表明，IL-10与EPO协同作用，在体外显著增强对红系分化和增殖的刺激，并且可能参与体内正常红细胞生成的调节。
