Abstract
This study was designed to investigate the neutrophil-targeted anti-inflammatory potential of posaconazole (0.1-5 microM, equivalent to 0.7-3.9 mg/L) by measuring the effects of this agent on the release of leukotriene B(4) (LTB(4)) and store-operated uptake of Ca(2+) following stimulation of human neutrophils with platelet-activating factor (200 nM). LTB(4) release and uptake of Ca(2+) by the cells were measured using an enzyme immunoassay and fura-2/AM-based spectrofluorimetric procedures, respectively. Treatment of neutrophils with posaconazole resulted in dose-related attenuation of PAF-activated release of LTB(4) and influx of Ca(2+), which attained statistical significance at 1 microM of the antimycotic. Although primarily an antimycotic, posaconazole possesses secondary anti-inflammatory activities, which may contribute to the therapeutic efficacy of this agent in patients with sepsis.
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