EFFECT OF CYTOKINES IN HOST DEFENSE AND INFLAMMATION

本项目的目的是研究细胞因子对宿主的影响。 防御和对吞噬细胞功能的影响。干扰素γ(干扰素-g) 纠正氧化代谢异常和杀菌杀菌 慢性阻塞性肺疾病患者中性粒细胞和单核细胞活性的研究 儿童肉芽肿性疾病(CGD)，无论是在体内还是在 在试管中。127名CGD患者(NIH的27名)进入双盲试验 隔日预防性应用干扰素-g的疗效观察(0.05) Mg/平方米)预防感染。干扰素-g给药减少 感染发生率降低了70%，住院天数减少了 确实发生了感染。干扰素-g体外处理正常单核细胞 膜和细胞质的mRNA转录本和蛋白水平增加 NADPH氧化酶组分，而白细胞介素4(IL-4)显著下降 这些组件。P47-Phox氧化酶成分增加或减少 多于其他组件，表明该组件是最关键的 在细胞因子对氧化酶活性的调节中。干扰素-g可诱导 应用氧化酶法诱导HL-60髓系白血病细胞分化 容量。在这种分化期间，出现了最戏剧性的增长 P47-Phox出现最慢，而p67-Phox出现最慢。在其他研究中 高免疫球蛋白E患者和反复感染患者的B细胞 (工作)综合症(HIE)显示出异常高的自发性 干扰素-g对小鼠免疫球蛋白E体外合成的影响 体外或体内。也产生了IgG1、3和4，但不产生IgG2或IgM 干扰素-g降低。在其他研究中，CGD单核细胞在体外形成 肉芽肿和这些肉芽肿可以用类固醇消散。

The purpose of this project is to study effects of cytokines upon host defense and upon phagocytic cell function. Interferon gamma (IFN-g) corrected abnormal oxidative metabolism and bactericidal and fungicidal activity of neutrophils and monocytes from patients with chronic granulomatous diseases of childhood (CGD) whether administered in vivo or in vitro. 127 CGD patients (27 at NIH) were entered into a double blinded study of the efficacy of every other day prophylactic IFN-g (0.05 mg/square-meter) in preventing infection. IFN-g administration decreased the incidence of infection by 70% and decreased hospital days for those infections which did occur. Normal monocytes treated in vitro with IFN-g increased mRNA transcripts and protein levels of membrane and cytoplasmic NADPH oxidase components, while Interleukin 4 (IL-4) markedly decreased these components. The p47-phox oxidase component increased or decreased more than other components, indicating that this component is most critical in cytokine regulation of oxidase activity. IFN-g can induce differentiation of HL-60 myeloid leukemia cells with acquisition of oxidase capacity. During such differentiation the most dramatic increase was seen with p47-phox, while p67-phox appeared most slowly. In other studies B-cells from patients with Hyperimmunoglobulin E and Recurrent Infections (Job's) Syndrome (HIE) were shown to have abnormally high spontaneous in vitro synthesis of IgE which was decreased by administration of IFN-g in vitro or in vivo. Production of IgG1,3, and 4, but not IgG2 or IgM was also decreased by IFN-g. In other studies CGD monocytes in vitro formed granulomas and these granulomas could be dispersed with steroids.