INFANT ANTIFUNGAL DEFENSE--ROLE OF CYTOKINES & STEROIDS

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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.