M-1584. Bliss Independence Interaction Analysis of the Inhibitory Effects of Hydrocortisone and Glucose on Human Neutrophil Mediated Hyphal Damage to Rhizopus oryzae
Session: Poster Session: Fungal Immunopathogenesis
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: Zygomycosis is more frequent in patients receiving corticosteroids, which cause both immunosuppression and hyperglycemia. The relative contributions of these two factors on host defenses against zygomycosis are not well understood. We therefore studied the inhibitory effects of hydrocortisone (HC) and glucose (GL) on the human neutrophils (PMNs) to damage hyphae of Rhizopus oryzae (RO). Methods: PMNs were isolated from healthy donors by elutriation. Fungal metabolism was measured by XTT assay after exposure of RO hyphae to glucose, hydrocortisone and PMNs alone, in double or triple combination with RO. GL (0, 80, 400, 800 and 3200 ug/ml) was combined with HC (0, 30, 300, 3000 and 30,000 uM) and PMNs (E:T ratio 20:1) against RO hyphae. The % hyphal metabolism was determined with XTT and calculated by comparison to control. Interactions were analyzed with Bliss independence interaction analysis where experimental % growth inhibition (IEXP) was compared with the theoretical one (ITHE) calculated as IGLU+IHCS+IPMN- (IGLUxIHCS + IGLUxIPMN + IHCSxIPMN). Synergy, antagonism and independence were defined when IEXP was significantly greater than, less than and equal to ITHE, respectively. Results: The combination of HC and GL slightly increased hyphal metabolism (7-15%). Hydrocortisone antagonized PMNs by 11-41% at concentrations >300uM (p < 0.05). This antagonistic interaction was not further affected by glucose (p > 0.10). Conclusion: The combination of HC, and glucose is antagonistic against PMN-induced hyphal damage of RO. As this antagonism is mainly due to the interaction between PMNs and HC, stringent clinical control of glucose may not further improve PMN function against RO.
C Antachopoulos, Aristotle Univ, D Kontoyiannis, MD, MD Anderson Cancer Center, Houston, TX, E Roilides, MD, PhD, Hellenic Study Group for the Susceptibility of S pneumoniae 2004, Haidari, Greece, J Meletiadis, Univ. Athens, Joanne Demchok, MS, National Institutes of Health, Behtesda, MD, T Stergiopoulou, NCI, T Walsh, MD, National Cancer Institute, Bethesda, MD and  J. P. Demchok, None.


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