Fluconazole increases bactericidal activity of neutrophils through non--cytokine-mediated pathway.
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.
Zervos
E E
EE
Department of Surgery, University of South Florida, Tampa, USA.
Fink
G W
GW
Norman
J G
JG
Robson
M C
MC
Rosemurgy
A S
AS
D000935:Antifungal Agents / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D016207:Cytokines / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000935:Antifungal Agents; D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015725:Fluconazole