Attenuation of airway obliteration by ciprofloxacin in experimental posttransplant bronchiolitis obliterans.
BACKGROUND
Ciprofloxacin is widely used to treat respiratory tract infections. Like other fluoroquinolones, ciprofloxacin has immunomodulatory effects; however, it is unknown whether these effects are beneficial in the setting of lung transplantation. We investigated potential immunomodulatory effects of ciprofloxacin in a model of posttransplant bronchiolitis obliterans.


METHODS
The heterotopic tracheal transplantation model in rats was used. Three groups received ciprofloxacin and underwent different immunosuppressive regimens of cyclosporine A, that is, no immunosuppression, insufficient immunosuppression, or low-dose immunosuppression. Three groups underwent the same immunosuppressive regimen but had no ciprofloxacin treatment. Tracheas were harvested after 21 days and examined with respect to histology and expression of selected cytokines.


RESULTS
The allografts of animals treated with ciprofloxacin showed less airway obliteration compared with allografts of untreated animals. When combined with low-dose immunosuppression ciprofloxacin showed beneficial effects in preventing airway obliteration and rejection of the respiratory epithelium. Cytokine gene expression of the allografts treated with ciprofloxacin was higher with respect to transforming growth factor-beta and equal with respect to tumor necrosis factor-alpha and interferon-gamma compared with controls. When applied in combination with cyclosporine A, ciprofloxacin lowered the expression of transforming growth factor-beta and tumor necrosis factor-alpha and increased interferon-gamma expression.


CONCLUSIONS
Ciprofloxacin attenuates airway rejection after tracheal transplantation. Genetic expression of mediators that are known to play an important role in mediating rejection in this model supports an immunomodulatory and antifibrotic role of ciprofloxacin. These findings suggest that further clinical studies are needed to investigate whether ciprofloxacin in addition to its bactericidal effect might be beneficial in the treatment of human posttransplant bronchiolitis obliterans.
Remund
Kaspar
K
Division of Pulmonary Medicine, University Hospital Zurich, Zurich, Switzerland.
Rechsteiner
Thomas
T
Rentsch
Katharina
K
Vogt
Peter
P
Russi
Erich W
EW
Boehler
Annette
A
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000188:drug therapy*; D002939:Ciprofloxacin / Q000097:blood / Q000627:therapeutic use*; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D008297:Male; D011183:Postoperative Complications / Q000188:drug therapy*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000637:transplantation*; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous / Q000473:pathology / Q000502:physiology*
D007166:Immunosuppressive Agents; D002939:Ciprofloxacin; D012313:RNA; D016572:Cyclosporine