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）。HIV感染相关的血细胞减少症 可能会通过增加对输血的暴露而影响患者的健康， 通过诱发细菌感染或出血，或通过限制 治疗选择，如抗逆转录病毒疗法。 制止 HIV感染者造血可能是骨髓感染的结果 辅助细胞，支持和调节造血，感染 造血祖细胞本身或两者。抗逆转录病毒治疗可能 加剧了这些影响。广泛的调查表明， 介导免疫应答的细胞因子，如白细胞介素-1，肿瘤 坏死因子和干扰素，产生贫血， 慢性炎症性疾病这些细胞因子的作用发生在几个 水平，包括造血祖细胞抑制和 适当的生长因子生产。在这个实验中要检验的假设 HIV感染中红细胞生成的抑制导致 从同样的机制，艾滋病毒感染本身可能会改变 造血祖细胞对生长因子的敏感性， 细胞因子 该假设将通过测定骨髓 HIV感染者的细胞因子水平;通过评估细胞因子/ HIV患者造血祖细胞生长因子反应性的研究 相对于非HIV感染个体，包括细胞因子的校正 造血生长因子介导的红细胞生成抑制; 评价抗逆转录病毒药物对细胞因子/生长因子的影响 来自HIV患者的造血祖细胞对 非HIV感染者;并通过确定 抗逆转录病毒药物对促红细胞生成素与高纯度人 红系祖细胞这些研究中提出的方法将提供 对HIV造血抑制机制的新认识 感染，并可能直接研究治疗方式 从而提高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.