HEMATOPOIETIC SUPPRESSION IN HIV INFECTION

外周血细胞减少症常见于人类感染 免疫缺陷病毒(HIV)。与HIV感染相关的细胞减少症 可能会通过增加对输液的接触而影响患者的健康， 通过易于细菌感染或出血，或通过限制 治疗选择，如抗逆转录病毒治疗。打压 HIV感染中的造血功能可能是骨髓感染所致 支持和调节造血、感染的辅助细胞 造血祖本身，或者两者兼而有之。抗逆转录病毒治疗可能 加剧了这些影响。广泛的调查表明， 介导免疫反应的细胞因子，如白介素1、肿瘤 坏死因子和干扰素会产生与以下相关的贫血 慢性炎症性疾病。这些细胞因子效应发生在几个 水平，包括造血祖细胞抑制和抑制 适度生产生长因子。这里要检验的假设是 建议是抑制艾滋病毒感染中的红细胞生成的结果 来自相同的机制，艾滋病毒感染本身可能改变 造血祖细胞对生长因子和 细胞因子。这一假说将通过骨髓测定来检验。 HIV感染者的细胞因子水平；通过评估细胞因子/ HIV患者造血祖细胞的生长因子反应性 相对于非艾滋病毒感染者，包括细胞因子的纠正 造血生长因子介导的抑制红细胞生成作用； 抗逆转录病毒药物对细胞因子/生长因子影响的评价 人类免疫缺陷病毒感染者造血祖细胞的反应性 未感染艾滋病毒的人；并通过确定 抗逆转录病毒药物对高纯度人促红细胞生成素结合的影响 红系祖细胞。这些研究中建议的方法将提供 人类免疫缺陷病毒抑制造血机制的新认识 感染，以及潜在的直接研究治疗方式 从而提高了这些患者的生活质量。

Peripheral blood cytopenias are commonly found in infection with the human immunodeficiency virus (HIV). The cytopenias associated with HIV infection may affect the health of patients by increasing exposure to transfusions, by predisposing to bacterial infection or bleeding, or by limiting therapeutic options such as antiretroviral therapy. Suppression of hematopoiesis in HIV infection may result from infection of marrow accessory cells which support and regulate hematopoiesis, infection of hematopoietic progenitors themselves, or both. Antiretroviral therapy may exacerbate these effects. Extensive investigation has indicated that the cytokines mediating the immune response, such as interleukin-1, tumor necrosis factor, and the interferons, produce the anemia associated with chronic inflammatory disorders. These cytokine effects occur at several levels, including hematopoietic progenitor suppression and inhibition of appropriate growth factor production. The hypothesis to be tested in this proposal is that suppression of erythropoiesis in HIV infection results from the same mechanism, and that HIV infection itself may alter the susceptibility of hematopoietic progenitors to growth factors and cytokines. The hypothesis will be tested by determination of marrow cytokine levels in HIV-infected individuals; by assessment of cytokine/ growth factor responsiveness of hematopoietic progenitors from HIV patients relative to non-HIV infected individuals, including correction of cytokine mediated inhibition of erythropoiesis by hematopoietic growth factors; by evaluating the effects of antiretroviral agents on cytokine/growth factor responsiveness of hematopoietic progenitors from HIV patients relative to non-HIV infected individuals; and by determining the effects of antiretroviral agents on erythropoietin binding to highly purified human erythroid progenitors. The approach proposed in these studies will provide new insight into the mechanisms of hematopoietic suppression in HIV infection, and potentially direct research into therapeutic modalities resulting in enhanced quality of life for these patients.