JOURNAL ARTICLE

Anti-inflammatory effects of moxifloxacin on IL-8, IL-1beta and TNF-alpha secretion and NFkappaB and MAP-kinase activation in human monocytes stimulated with Aspergillus fumigatus

Itamar Shalit, Drora Halperin, Debby Haite, Avital Levitov, Jacob Romano, Nir Osherov, Ina Fabian
Journal of Antimicrobial Chemotherapy 2006, 57 (2): 230-5
16352735

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 1.5x10(6)/mL conidia of a clinical isolate of A. fumigatus. Cytokine secretion and activation of NFkappaB 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-1beta and TNF-alpha 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-NFkappaB protein expression by 1.6-, 1.3- and 1.8-fold, respectively. Addition of moxifloxacin inhibited ERK1/2, p38 and p65-NFkappaB 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 with A. 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.

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