Schwarzenberger P, La Russa V, Miller A, Ye P, Huang W, Zieske A, Nelson S, Bagby G J, Stoltz D, Mynatt R L, Spriggs M, Kolls J K
Department of Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
J Immunol. 1998 Dec 1;161(11):6383-9.
IL-17 is a novel cytokine secreted principally by CD4+ T cells. It has been shown to support the growth of hemopoietic progenitors in vitro; however, its in vivo effects are presently unknown. Adenovirus-mediated gene transfer of the murine IL-17 cDNA targeted to the liver (5 x 10(9) plaque-forming units (PFU) intravenous) resulted in a transiently transgenic phenotype, with dramatic effects on in vivo granulopoiesis. Initially, there was a significant increase (fivefold) in the peripheral white blood count (WBC), including a 10-fold rise in the absolute neutrophil count. This was associated with a doubling in the spleen size over 7-14 days after gene transfer, which returned to near baseline by day 21, although the white blood cell count remained elevated. There was a profound stimulation of splenic hemopoiesis as demonstrated by an increase in total cellularity by 50% 7 days after gene transfer and an increase in hemopoietic colony formation. A maximal increase in frequency of high proliferative potential colonies (HPPC) (11-fold) and CFU-granulocyte-macrophage (GM) and CFU-granulocyte-erythrocyte-megakaryocyte-monocyte (GEMM) (CFU) (6-fold) was seen on day 3 after IL-17 gene transfer. Both CFU and HPPC remained significantly elevated in the spleen throughout day 21, but at reduced levels compared with day 3. Bone marrow CFU and HPPC were elevated on day 3 only by 75% and 25%, respectively, without changes in total cellularity. Thus, murine IL-17 is a cytokine that can stimulate granulopoiesis in vivo. Since IL-17 is principally produced by CD4+ T cells, this cytokine could have therapeutic implications in AIDS-related bone marrow failure and opportunistic infections.
白细胞介素-17（IL-17）是一种主要由CD4 + T细胞分泌的新型细胞因子。已表明它在体外可支持造血祖细胞的生长；然而，其体内作用目前尚不清楚。将靶向肝脏的小鼠IL-17 cDNA通过腺病毒介导的基因转移（静脉注射5×10⁹ 噬斑形成单位（PFU））导致了一种短暂的转基因表型，对体内粒细胞生成产生显著影响。最初，外周白细胞计数（WBC）显著增加（五倍），包括绝对中性粒细胞计数增加了10倍。这与基因转移后7 - 14天脾脏大小加倍有关，尽管白细胞计数仍保持升高，但到第21天时脾脏大小恢复到接近基线水平。基因转移7天后，脾脏总细胞数增加50%，造血集落形成增加，表明脾脏造血受到深刻刺激。IL-17基因转移后第3天，高增殖潜能集落（HPPC）（11倍）以及集落形成单位-粒细胞-巨噬细胞（CFU-GM）和集落形成单位-粒细胞-红细胞-巨核细胞-单核细胞（GEMM）（CFU）（6倍）的频率出现最大增加。在第21天全天，脾脏中的CFU和HPPC均显著升高，但与第3天相比水平降低。骨髓CFU和HPPC仅在第3天分别升高了75%和25%，总细胞数无变化。因此，小鼠IL-17是一种可在体内刺激粒细胞生成的细胞因子。由于IL-17主要由CD4 + T细胞产生，这种细胞因子可能对艾滋病相关的骨髓衰竭和机会性感染具有治疗意义。
