FLUCONAZOLE INCREASES BACTERICIDAL ACTIVITY OF NEUTROPHILS THROUGH NON-CYTOKINE-MEDIATED PATHWAY

Background: Polymorphonuclear neutrophils (PMNs) preincubated with flu conazole (FCZ) demonstrate enhanced bactericidal activity in vitro. Ob jective: This study was undertaken to determine the role of cytokines in FCZ-induced augmentation of PMN function. Methods: PMNs were preinc ubated with PBS or FCZ and exposed to Escherichia coli, Cell culture s upernatants and mRNA were isolated after preincubation and again after exposure to E. coli, Tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-8 protein and mRNA levels were determined using enzyme-li nked immunosorbent assay and polymerase chain reaction, respectively. Results were compared using the Student's t test. Results: Preincubati on of PMNs with FCZ resulted in enhanced killing but no difference in cytokine protein or mRNA levels when compared to control, After exposu re to E. coli, PMNs significantly up-regulate IL-8 and tumor necrosis factor-alpha independent of the solution with which they were preincub ated. Conclusions: Up-regulation of the cytokine cascade plays a minor role, at most, in the mechanism through which FCZ augments the bacter icidal activity of PMNs.