Blazar B R, Widmer M B, Taylor P A, Vallera D A
Department of Pediatrics, University of Minnesota Hospital and Clinic, Minneapolis.
Blood. 1992 Sep 15;80(6):1614-22.
Irradiated C57BL/6 (H-2b) recipients of T-cell-depleted (TCD) BALB/c (H-2d) bone marrow (BM) and recombinant interleukin-1 alpha (IL-1 alpha) (1 microgram/d) had a significantly (P less than or equal to .006) higher 100-day actuarial survival rate, accelerated hematopoietic recovery, and higher levels of alloengraftment than a group of transplanted control mice treated identically, but given phosphate-buffered saline (PBS). To elucidate the mechanisms involved with IL-1 alpha-induced promotion of alloengraftment and hematopoietic recovery, we performed sequential splenic FACS studies on transplanted mice and secondary transfer studies in syngeneic mice given IL-1 alpha or PBS. Splenic phenotyping showed that recipients of IL-1 alpha had a higher proportion of donor granulocytes (52% v 19%) as compared with PBS controls as early as 7 days after bone marrow transplantation (BMT). On day 11 post-BMT, recipients of IL-1 alpha had a more than fourfold increase in splenocyte number, which included a higher percentage (90% v 59%) of donor cells, especially donor granulocytes (52% vs 32%), and a sevenfold increase in donor T cells as compared with controls. Host T-cell numbers were not affected. Taken together, these data suggest that IL-1 alpha stimulated bipotential (myeloid and lymphoid) donor cell engraftment. In a syngeneic BMT system, administration of IL-1 alpha resulted in a higher incidence of survival when recipients were transplanted with BM cells, indicating that IL-1 alpha administration probably either expanded or potentiated engraftment of a committed progenitor cell pool. Secondary transfer experiments using marrow from IL-1 alpha-treated mice showed that the number of day 12 colony-forming unit-spleen (CFU-S) cells was unaltered compared with untreated control mice, suggesting that more primitive, albeit committed, hematopoietic progenitor cells were not affected. We also examined the potential additive effects of IL-1 alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) administered in combination (for 14 days). Mice receiving a suboptimal amount of IL-1 alpha along with GM-CSF had significantly higher levels of donor alloengraftment (92%) with superior hematopoietic recovery, as compared with mice receiving either IL-1 alpha (57%) or GM-CSF (18%) alone.
接受T细胞去除（TCD）的BALB/c（H-2d）骨髓（BM）移植且每日注射重组白细胞介素-1α（IL-1α）（1微克/天）的经辐照C57BL/6（H-2b）受体，其100天精算生存率显著更高（P≤0.006），造血恢复加快，且同种异体植入水平高于一组接受相同处理但注射磷酸盐缓冲盐水（PBS）的移植对照小鼠。为阐明IL-1α诱导同种异体植入和造血恢复促进作用的机制，我们对移植小鼠进行了连续的脾脏荧光激活细胞分选（FACS）研究，并在注射IL-1α或PBS的同基因小鼠中进行了二次移植研究。脾脏表型分析显示，早在骨髓移植（BMT）后7天，与PBS对照组相比，接受IL-1α的受体中供体粒细胞比例更高（52%对19%）。在BMT后第11天，接受IL-1α的受体脾细胞数量增加了四倍多，其中供体细胞百分比更高（90%对59%），尤其是供体粒细胞（52%对32%），且供体T细胞数量比对照组增加了七倍。宿主T细胞数量未受影响。综合来看，这些数据表明IL-1α刺激了双能（髓系和淋巴系）供体细胞的植入。在同基因BMT系统中，当受体接受BM细胞移植时，注射IL-1α导致更高的生存率，这表明注射IL-1α可能扩大或增强了定向祖细胞池的植入。使用来自经IL-1α处理小鼠的骨髓进行的二次移植实验表明，与未处理的对照小鼠相比，第12天脾集落形成单位（CFU-S）细胞数量未改变，这表明更原始的定向造血祖细胞未受影响。我们还研究了联合注射IL-1α和粒细胞-巨噬细胞集落刺激因子（GM-CSF）（共14天）的潜在相加效应。与单独接受IL-1α（57%）或GM-CSF（18%）的小鼠相比，接受次优剂量IL-1α与GM-CSF联合治疗的小鼠具有显著更高水平的供体同种异体植入（92%）和更好的造血恢复。
