Anti-inflammatory effects of antibacterials on human Bronchial epithelial cells.
BACKGROUND
Human Bronchial epithelial cells (hu-BEC) have been claimed to play a significant role in the pathogenesis of chronic inflammatory airway diseases like COPD. In this context IL-8 and GM-CSF have been shown to be key cytokines. Some antibiotics which are routinely used to treat lower respiratory tract infections have been shown to exert additional immunomodulatory or anti-inflammatory effects. We investigated whether these effects can also be detected in hu-BEC.


METHODS
Hu-BEC obtained from patients undergoing lung resections were transferred to air-liquid-interface (ALI) culture. These cultures were incubated with cefuroxime (CXM, 10-62.5 mg/l), azithromycin (AZM, 0.1-1.5 mg/l), levofloxacin (LVX, 1-8 mg/l) and moxifloxacin (MXF, 1-16 mg/l). The spontaneous and TNF-alpha (10 ng/ml) induced expression and release of IL-8 and GM-CSF were measured using PCR and ELISA in the absence or presence of these antibiotics.


RESULTS
The spontaneous IL-8 and GM-CSF release was significantly reduced with MXF (8 mg/l) by 37 +/- 20% and 45 +/- 31%, respectively (both p < 0.01). IL-8 release in TNF-alpha stimulated hu-BEC decreased by 16 +/- 8% (p < 0.05) with AZM (1.5 mg/l). With MXF a concentration dependent decrease of IL-8 release was noted up to 39 +/- 7% (p < 0.05). GM-CSF release from TNF-alpha stimulated hu-BEC was maximally decreased by 35 +/- 24% (p < 0.01) with MXF (4 mg/l).


CONCLUSIONS
Using ALI cultures of hu-BEC we observed differential effects of antibiotics on spontaneous and TNF-alpha induced cytokine release. Our data suggest that MXF and AZM, beyond bactericidal effects, may attenuate the inflammatory process mediated by hu-BEC.
Department of Internal Medicine I, Division of Pulmonary Diseases, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany. Gregor.Zimmermann@med.uni-muenchen.de
Gregor S
GS
Zimmermann
Claus
C
Neurohr
Heidrun
H
Villena-Hermoza
Rudolf
R
Hatz
Juergen
J
Behr
D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha