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


METHODS
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.


RESULTS
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.


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.
Steel
H C
HC
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.
Theron
A J
AJ
Tintinger
G R
GR
Anderson
R
R
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007155:Immunologic Factors / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000276:immunology; D013050:Spectrometry, Fluorescence / Q000379:methods; D014230:Triazoles / Q000494:pharmacology*; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D010972:Platelet Activating Factor; D014230:Triazoles; D007975:Leukotriene B4; C101425:posaconazole; D002118:Calcium