INFANT ANTIFUNGAL DEFENSE--ROLE OF CYTOKINES & STEROIDS

研究计划白色念珠菌是一种主要的机会性真菌， 在高危人群中产生危及生命的疾病，例如LBW婴儿。 有效的白念珠菌宿主防御需要激活细胞因子 白细胞。据推测，LBW婴儿有罹患C. 白念珠菌是因为他们的白细胞对细胞因子的反应较差 激活。进一步推测，白念珠菌的转变 从共生菌到致病微生物受 免疫效应细胞的荷尔蒙环境。类固醇激素 (糖皮质激素-GC；雌激素-E；孕酮-P；睾酮-T)是 能够在免疫细胞功能和激活方面产生强有力的变化， 而这些激素可能会改变白细胞的AFA。类固醇调节血管紧张素转换酶的作用 AFA可能是严重应激婴儿免疫反应受损的基础 疾病，也可能解释了白细胞AFA的性别差异。 体重/婴儿。婴儿脐带血中的白细胞将被分离成 多形核细胞、巨噬细胞和淋巴细胞与 细胞因子激活剂，AFA将通过测量依从性和 抑制白色念珠菌的生长。类固醇(GC、E、P&T)的作用 将在基础和细胞因子激活的白细胞中测量对AFA的影响。 AFA与新生儿出生体重、性别、产前GC、 和病情严重程度(新生儿急性生理学评分；SNAP) 下定决心。了解抗真菌的潜力和影响因素 调节低出生体重儿白细胞的AFA对预测 有真菌感染风险的婴儿和发展有效的婴儿 保护低出生体重儿免受白念珠菌感染的策略。这样的研究并没有 之前已完成，并将提供对效果的新见解 神经内分泌系统对机会性真菌免疫反应的影响 易感人群中的感染。

Research Plan Candida albicans is a major opportunistic fungus that produces life-threatening disease in high risk groups, such as LBW infants. Effective host defense against C. albicans requires cytokine activation of leukocytes. It is hypothesized that LBW infants are at risk for C. albicans because their leukocytes are less responsive to cytokine activation. It is further hypothesized that the transition of C. albicans from a commensal to a pathogenic microorganism is influenced by the hormonal milieu of immune effector cells. Steroid hormones (glucocorticoids-GC; estrogens-E; progesterone-P; testosterone-T) are capable of producing potent changes in immune cell function and activation, and these hormones may alter leukocyte AFA. Steroid-mediated modulation of AFA may underlie the impaired immune response of infants stressed by severe illness and may also account for gender differences in leukocyte AFA of LBW/infants. Leukocytes from cord blood of infants will be separated into polymorphonuclear cells, macrophages, and lymphocytes and cultured with cytokine activators, AFA will be assessed by measuring adherence to and growth inhibition of C. albicans. The effect of steroids (GC, E, P, & T) on AFA will be measured in basal and cytokine-activated leukocytes. Relationships between AFA and infant birth weight, gender, antenatal GC, and severity of illness (Score for Acute Neonatal Physiology; SNAP) will be determined. Knowledge of the antifungal potential and the factor that modulate AFA of leukocytes from LBW infants is crucial for predicting infants at risk for fungal infections and for developing effective strategies to protect LBW infants from C. albicans. Such studies have not been accomplished previously and will provide new insights into the effect of the neuroendocrine system on the immune response to opportunistic fungal infections in vulnerable populations.