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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01NR000085-02
Application #
2519819
Study Section
National Institute of Nursing Research Initial Review Group (NRRC)
Program Officer
Sigmon, Hilary D
Project Start
1996-09-01
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Loyola University Chicago
Department
Type
Schools of Nursing
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
Witek-Janusek, Linda; Shareef, Maliha J; Mathews, Herbert L (2002) Reduced lymphocyte-mediated antifungal capacity in high-risk infants. J Infect Dis 186:129-33
Nagabhushan, M; Mathews, H L; Witek-Janusek, L (2001) Aberrant nuclear expression of AP-1 and NFkappaB in lymphocytes of women stressed by the experience of breast biopsy. Brain Behav Immun 15:78-84
Witek-Janusek, L; Mathews, H L (1999) Differential effects of glucocorticoids on colony stimulating factors produced by neonatal mononuclear cells. Pediatr Res 45:224-9
Shareef, M J; Myers, T F; Mathews, H L et al. (1999) Reduced capacity of neonatal lymphocytes to inhibit the growth of Candida albicans. Biol Neonate 75:31-9
Witek-Janusek, L; Stoddard, J; Mathews, H L (1998) Trauma-induced immune dysfunction: a challenge for critical care. Dimens Crit Care Nurs 17:187-99
Mathews, H L; Witek-Janusek, L (1998) Antifungal activity of interleukin-2-activated natural killer (NK1.1+) lymphocytes against Candida albicans. J Med Microbiol 47:1007-14
Mathews, H L; Conti, S; Witek-Janusek, L et al. (1998) Effect of Pichia anomala killer toxin on Candida albicans. Med Mycol 36:199-204
Witek-Janusek, L; Cusack, C; Mathews, H L (1998) Candida albicans: an opportunistic threat to critically ill low birth weight infants. Dimens Crit Care Nurs 17:243-55