Morrissey P J, Conlon P, Braddy S, Williams D E, Namen A E, Mochizuki D Y
Immunex Corporation, Seattle, WA 98101.
J Immunol. 1991 Mar 1;146(5):1547-52.
Lymphopenia was induced in mice by a single injection of cyclophosphamide. IL-7 or a control protein were administered to the mice twice daily and the cellularity and composition of the spleen, lymph node, bone marrow, and thymus were determined at various time points thereafter. In comparison to the control cyclophosphamide-treated mice, animals receiving cyclophosphamide and IL-7 had an accelerated regeneration of splenic and lymph node cellularity. There was no significant difference in the rate of recovery of the bone marrow and thymus of the control and IL-7-treated mice. Assessment of the pre-B cell compartment revealed a dramatic increase in total pre-B cell numbers in the spleen and bone marrow of the IL-7-treated mice as measured by both flow microfluorimetry and a pre-B cell colony-forming assay. This was followed in a few days by a significant increase in surface IgM+B cell numbers to levels above normal values in both the spleen and lymph node. IL-7 administration to cyclophosphamide-treated mice also resulted in an accelerated recovery of peripheral CD4+ and CD8+ cell numbers in the spleen and lymph node. The numbers of CD8+ cells were increased by twofold over normal levels in cyclophosphamide-treated mice receiving IL-7. Myeloid recovery was determined in cyclophosphamide treated mice by assessing the numbers of CFU-granulocyte-macrophage and Mac 1+ cells. There was no significant difference in myeloid recovery between cyclophosphamide-treated mice receiving IL-7 or control protein. These results suggest that administration of IL-7 after chemical-induced lymphopenia may have therapeutic benefits in shortening the period required to achieve normal lymphoid cellularity.
通过单次注射环磷酰胺在小鼠中诱导淋巴细胞减少。每天给小鼠两次注射白细胞介素-7(IL-7)或对照蛋白,然后在不同时间点测定脾脏、淋巴结、骨髓和胸腺的细胞数量及组成。与环磷酰胺处理的对照小鼠相比,接受环磷酰胺和IL-7的动物脾脏和淋巴结细胞数量的再生加速。对照小鼠和接受IL-7处理的小鼠骨髓和胸腺的恢复速率没有显著差异。对前B细胞区室的评估显示,通过流式微量荧光测定法和前B细胞集落形成试验测量,接受IL-7处理的小鼠脾脏和骨髓中前B细胞总数显著增加。几天后,脾脏和淋巴结中表面IgM+B细胞数量显著增加至高于正常值的水平。给环磷酰胺处理的小鼠注射IL-7还导致脾脏和淋巴结中外周CD4+和CD8+细胞数量加速恢复。在接受IL-7的环磷酰胺处理小鼠中,CD8+细胞数量比正常水平增加了两倍。通过评估集落形成单位-粒细胞-巨噬细胞(CFU-粒细胞-巨噬细胞)和Mac 1+细胞的数量,在环磷酰胺处理的小鼠中测定髓系恢复情况。接受IL-7或对照蛋白的环磷酰胺处理小鼠之间的髓系恢复没有显著差异。这些结果表明,化学诱导淋巴细胞减少后给予IL-7可能在缩短达到正常淋巴细胞数量所需时间方面具有治疗益处。