title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. shalit_i@netvision.net.il
authors.forename: Itamar
authors.initials: I
authors.lastname: Shalit
authors.forename: Drora
authors.initials: D
authors.lastname: Halperin
authors.forename: Debby
authors.initials: D
authors.lastname: Haite
authors.forename: Avital
authors.initials: A
authors.lastname: Levitov
authors.forename: Jacob
authors.initials: J
authors.lastname: Romano
authors.forename: Nir
authors.initials: N
authors.lastname: Osherov
authors.forename: Ina
authors.initials: I
authors.lastname: Fabian
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000502:physiology*; D001372:Aza Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D024841:Fluoroquinolones; D006801:Humans; D007165:Immunosuppression Therapy; D007375:Interleukin-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000077266:Moxifloxacin; D016328:NF-kappa B / Q000378:metabolism*; D016759:Oncogene Protein p65(gag-jun) / Q000235:genetics / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001372:Aza Compounds; D024841:Fluoroquinolones; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D016759:Oncogene Protein p65(gag-jun); D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077266:Moxifloxacin