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JAC Advance Access originally published online on September 10, 2009
Journal of Antimicrobial Chemotherapy 2009 64(5):1008-1012; doi:10.1093/jac/dkp329
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

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

H. C. Steel, A. J. Theron, G. R. Tintinger and R. Anderson*

Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa

Received 31 March 2009; returned 29 July 2009; revised 12 August 2009; accepted 13 August 2009

* Corresponding author. Tel: +27-12-319-2425; Fax: +27-12-323-0732; E-mail: randerso{at}medic.up.ac.za

Objectives: This study was designed to investigate the neutrophil-targeted anti-inflammatory potential of posaconazole (0.1–5 µM, equivalent to 0.7–3.9 mg/L) by measuring the effects of this agent on the release of leukotriene B4 (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-activated release of LTB4 and influx of Ca2+, which attained statistical significance at 1 µM 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.

Keywords: clarithromycin , fMLP , itraconazole , 5-lipoxygenase , platelet-activating factor


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