Goldman S J
Genetics Institute, Andover, MA 01810, USA.
Stem Cells. 1995 Sep;13(5):462-71. doi: 10.1002/stem.5530130503.
Interleukin 11 (IL-11) is a multifunctional hematopoietic cytokine which was originally identified as a factor produced by an IL-1-stimulated primate stromal cell line. The in vitro biological activities of recombinant human (rHu)IL-11 result predominantly from synergistic interactions with other growth factors. In combination with other cytokines, rHuIL-11 has been shown to support the formation of primitive hematopoietic and lymphohematopoietic progenitor colonies from bone marrow, to promote erythroid burst formation and to stimulate both early and late stages of megakaryocyte proliferation and differentiation. rHuIL-11 is biologically active in mice, rats, dogs and primates when administered as a single agent in vivo. The predominant effect of rHuIL-11 in naive mice was on cells of the megakaryocytic lineage, increasing the number of bone marrow megakaryocyte progenitors, stimulating megakaryocyte endoreplication and increasing peripheral platelet counts in a dose-dependent fashion. Similar megakaryocytic stimulatory activity was seen in nonhuman primates treated with rHuIL-11 where platelet counts were increased by as much as 300%. In several models of severe myelosuppression induced by chemotherapy and/or irradiation and in bone marrow transplant models, there were multilineage hematopoietic stimulation following rHuIL-11 treatment. In these models, accelerated recovery of platelets was a consistent observation, while some models show enhanced neutrophil and red blood cell recovery as well. These results from preclinical studies confirm the broad spectrum of biological activities exhibited by rHuIL-11 in vitro, and suggest that this cytokine may be an effective agent in the treatment of myelosuppression and thrombocytopenia associated with cancer chemotherapy and bone marrow transplantation.
白细胞介素11（IL-11）是一种多功能造血细胞因子，最初被鉴定为一种由白细胞介素-1刺激的灵长类基质细胞系产生的因子。重组人（rHu）IL-11的体外生物学活性主要源于与其他生长因子的协同相互作用。与其他细胞因子联合使用时，rHuIL-11已被证明可支持从骨髓中形成原始造血和淋巴造血祖细胞集落，促进红系爆式集落形成，并刺激巨核细胞增殖和分化的早期及晚期阶段。当在体内作为单一药物给药时，rHuIL-11在小鼠、大鼠、狗和灵长类动物中具有生物学活性。rHuIL-11对未处理小鼠的主要作用是作用于巨核细胞系细胞，以剂量依赖的方式增加骨髓巨核细胞祖细胞数量，刺激巨核细胞内复制并增加外周血小板计数。在用rHuIL-11治疗的非人类灵长类动物中也观察到了类似的巨核细胞刺激活性，血小板计数增加了多达300%。在化疗和/或放疗诱导的严重骨髓抑制的几种模型以及骨髓移植模型中，rHuIL-11治疗后出现了多谱系造血刺激。在这些模型中，血小板加速恢复是一致的观察结果，而一些模型还显示中性粒细胞和红细胞恢复增强。这些临床前研究结果证实了rHuIL-11在体外表现出的广泛生物学活性，并表明这种细胞因子可能是治疗与癌症化疗和骨髓移植相关的骨髓抑制和血小板减少症的有效药物。
