ANALYSIS OF BMT CONDITIONING, CYTOKINES, GVHD AND GVL

产品说明：我们的初步数据表明，预处理方案的强度与显著放大GVHD的内毒素、TNF α和IL-1的全身水平相关。 使用小鼠BMT模型，我们建议研究新的策略来调节这种细胞因子级联反应，并确定个体靶器官病理学与系统性GVHD变化相关的程度。 我们的具体目标是：1） 探讨IL-11和角质细胞生长因子对强化条件异基因骨髓移植后GVHD的预防作用。（二） 比较异基因骨髓移植前预处理方案对炎性细胞因子的影响。第三章 分析直接和间接阻断炎性细胞因子作为区分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.