BACKGROUND: Polymorphonuclear neutrophils (PMNs) preincubated with fluconazole (FCZ) demonstrate enhanced bactericidal activity in vitro. OBJECTIVE: This study was undertaken to determine the role of cytokines in FCZ-induced augmentation of PMN function. METHODS: PMNs were preincubated with PBS or FCZ and exposed to Escherichia coli. Cell culture supernatants 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-linked immunosorbent assay and polymerase chain reaction, respectively. Results were compared using the Student's t test. RESULTS: Preincubation of PMNs with FCZ resulted in enhanced killing but no difference in cytokine protein or mRNA levels when compared to control. After exposure to E. coli, PMNs significantly up-regulate IL-8 and tumor necrosis factor-alpha independent of the solution with which they were preincubated. CONCLUSIONS: Up-regulation of the cytokine cascade plays a minor role, at most, in the mechanism through which FCZ augments the bactericidal activity of PMNs.
BACKGROUND: Polymorphonuclear neutrophils (PMNs) preincubated with fluconazole (FCZ) demonstrate enhanced bactericidal activity in vitro. OBJECTIVE: This study was undertaken to determine the role of cytokines in FCZ-induced augmentation of PMN function. METHODS: PMNs were preincubated with PBS or FCZ and exposed to Escherichia coli. Cell culture supernatants 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-linked immunosorbent assay and polymerase chain reaction, respectively. Results were compared using the Student's t test. RESULTS: Preincubation of PMNs with FCZ resulted in enhanced killing but no difference in cytokine protein or mRNA levels when compared to control. After exposure to E. coli, PMNs significantly up-regulate IL-8 and tumor necrosis factor-alpha independent of the solution with which they were preincubated. CONCLUSIONS: Up-regulation of the cytokine cascade plays a minor role, at most, in the mechanism through which FCZ augments the bactericidal activity of PMNs.
Authors: Mohammad Tariq; Ahmed Al Moutaery; Mohammed Arshaduddin; Haseeb Ahmad Khan; David Price Evans; Sydney Jacobs Journal: Intensive Care Med Date: 2003-09-27 Impact factor: 17.440