JAC Advance Access originally published online on December 13, 2005
Journal of Antimicrobial Chemotherapy 2006 57(2):230-235; doi:10.1093/jac/dki441
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Anti-inflammatory effects of moxifloxacin on IL-8, IL-1ß and TNF-
secretion and NF
B and MAP-kinase activation in human monocytes stimulated with Aspergillus fumigatus
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Received 8 April 2005; returned 15 September 2005; revised 1 October 2005; accepted 7 November 2005
* Correspondence address. Paediatric Infectious Diseases Unit, Schneider Children's Medical Centre of Israel, 14 Kaplan Street, Petach-Tikvah 49202, Israel. Tel: +972-3-9253206; Fax: +972-3-9247515; E-mail: shalit_i{at}netvision.net.il
Objectives: We have previously shown that moxifloxacin conferred protective anti-inflammatory effects against Candida pneumonia in immunosuppressed mice. Further in vitro studies showed anti-inflammatory effects of moxifloxacin in LPS and cytokine-stimulated monocytic and epithelial cells. In the present study, concentrating on a more challenging pathogen of immunosuppressed hosts, we studied the effect of moxifloxacin on cytokine secretion and signal transduction mechanisms in monocytic cells stimulated with Aspergillus fumigatus.
Methods: Human peripheral blood monocytes (PBMCs) and a human monocytic cell line (THP-1) were incubated with 1.5 x 106/mL conidia of a clinical isolate of A. fumigatus. Cytokine secretion and activation of NF
B and the MAP-kinases ERK1/2 and p38 were measured with and without the addition of moxifloxacin (5–20 mg/L).
Results: Stimulation of PBMCs and THP-1 cells with A. fumigatus increased IL-8, IL-1ß and TNF-
secretion (4.1-, 8.3- and 7-fold, and 5.4-, 3.7- and 17.8-fold, respectively). Addition of moxifloxacin (5–20 mg/L) inhibited cytokine secretion up to 45.7 ± 5%, 72 ± 13% and 73 ± 10% in PBMCs and up to 35.6 ± 0.5%, 30 ± 2.4% and 19 ± 4% in THP-1 cells (P < 0.05). Signal transduction studies showed that incubation of THP-1 cells with A. fumigatus increased ERK1/2 and p38 phosphorylation and p65-NFB protein expression by 1.6-, 1.3- and 1.8-fold, respectively. Addition of moxifloxacin inhibited ERK1/2, p38 and p65-NFB by up to 69 ± 14%, 58 ± 3% and 75 ± 15%, respectively.
Conclusions: Our results indicate that moxifloxacin acts as an anti-inflammatory agent in monocytic cells stimulated withA. fumigatus conidia. Whether these effects may be protective as in the Candida pneumonia model is unknown and merits in vivo studies in models of pulmonary aspergillosis.
Keywords: cytokines , aspergillosis , immunomodulation , A. fumigatus
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