Anti-inflammatory effects of moxifloxacin on IL-8, IL-1β and TNF-α secretion and NFkB 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 × 106/mL conidia of a clinical isolate of A. fumigatus. Cytokine secretion and activation of NFk;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-1β and TNF-α 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-NFkB protein expression by 1.6-, 1.3- and 1.8-fold, respectively. Addition of moxifloxacin inhibited ERK1/2, p38 and p65-NFkB 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.

Original languageEnglish
Pages (from-to)230-235
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume57
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • A. fumigatus
  • Aspergillosis
  • Cytokines
  • Immunomodulation

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