Posaconazole attenuates leukotriene B4 release and uptake of calcium by chemoattractant-activated human neutrophils: a potential strategy to control neutrophil-mediated inflammation

Objectives: This study was designed to investigate the neutrophil-targeted anti-inflammatory potential of posaconazole (0.1-5 mu M, equivalent to 0.7-3.9 mg/L) by measuring the effects of this agent on the release of leukotriene B-4 (LTB4) and store-operated uptake of Ca2+ following stimulation of human neutrophils with platelet-activating factor (200 nM). Methods: LTB4 release and uptake of Ca2+ by the cells were measured using an enzyme immunoassay and fura-2/AM-based spectrofluorimetric procedures, respectively. Results: Treatment of neutrophils with posaconazole resulted in dose-related attenuation of PAF-ctivated release of LTB4 and influx of Ca2+, which attained statistical significance at 1 mu M of the antimycotic. Conclusions: Although primarily an antimycotic, posaconazole possesses secondary anti-inflammatory activities, which may contribute to the therapeutic efficacy of this agent in patients with sepsis.