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，如LBW婴儿。 对C.白念珠菌需要细胞因子激活 白细胞 据推测，LBW婴儿有患C。 因为白细胞对细胞因子的反应较低 activation. 进一步假设C.白色 从细菌到病原微生物的转化受到 免疫效应细胞的激素环境。 类固醇激素 （糖皮质激素-GC;雌激素-E;孕酮-P;睾酮-T） 能够在免疫细胞功能和活化中产生强有力的变化， 这些激素可能改变白细胞AFA。 类固醇介导的 AFA可能是婴儿免疫反应受损的基础， 疾病，也可以解释白细胞AFA的性别差异， LBW/婴儿。 婴儿脐带血中的白细胞将被分离成 多形细胞、巨噬细胞和淋巴细胞，并与 细胞因子激活剂，AFA将通过测量对 生长抑制C.白色念珠菌 类固醇（GC，E，P，& T）的作用 将在基础白细胞和白细胞介素活化的白细胞中测量AFA。 AFA与婴儿出生体重、性别、产前GC、 和疾病严重程度（急性新生儿生理学评分; SNAP）将是 测定 了解抗真菌的潜力和 调节LBW婴儿白细胞AFA对于预测 有真菌感染风险的婴儿， 保护LBW婴儿免受C.白色念珠菌 这些研究没有 以前已经完成，并将提供新的见解的影响， 神经内分泌系统对机会性真菌免疫应答的影响 易感染人群。

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.