ANALYSIS OF BMT CONDITIONING, CYTOKINES, GVHD AND GVL

描述：(申请人描述)我们的初步数据显示，预适应方案的强度与系统内毒素、肿瘤坏死因子α和IL-1的水平相关，这些水平显著地放大了移植物抗宿主病。利用小鼠骨髓移植模型，我们建议研究调节这种细胞因子级联反应的新策略，并确定单个靶器官病理与全身性移植物抗宿主病的变化相关的程度。我们的具体目标是：1)评价IL-I-1和角质形成细胞生长因子对异基因骨髓移植后GVHD的预防作用。2)比较异基因骨髓移植前的预适应方案对炎性细胞因子的影响。3)分析炎性细胞因子的阻断(直接和间接)作为区分GVL和GVHD的策略。

DESCRIPTION: (Applicant's Description) Our preliminary data demonstrate that the intensity of the conditioning regimen correlates with systemic levels of endotoxin, TNFalpha and IL-1 which significantly amplify GVHD. Using murine BMT models, we propose to investigate novel strategies to modulate this cytokine cascade, and to determine the extent to which individual target organ pathology correlates with changes in systemic GVHD. Our specific aims are: 1) To evaluate the ability of IL-I 1 and keratinocyte growth factor to prevent GVHD after intensively conditioned allogeneic BMT. 2) To compare conditioning regimens prior to allogeneic BMT for their effects on inflammatory cytokines. 3) To analyze blockade of inflammatory cytokines (both directly and indirectly) as a strategy to separate GVL from GVHD.