Immunomodulatory effects of ciprofloxacin in TNBS-induced colitis in mice.
BACKGROUND
Crohn's exacerbation and pouchitis are commonly treated with ciprofloxacin and metronidazole. Few studies have shown an advantage of this regimen compared with other antibiotics. Most attributed the effect to its better antibacterial coverage. Others have shown an apparent anti-inflammatory effect of quinolones in several in vitro and in vivo models of inflammation other than inflammatory bowel diseases (IBD). Our objective was to test the hypothesis that ciprofloxacin may act as an anti-inflammatory agent rather than just an antibacterial drug using a model of chemical colitis.


METHODS
TNBS colitis was induced in BALB/c mice. The anti-inflammatory effect of ciprofloxacin compared with ceftazidime and dexamethasone was assessed.


RESULTS
Mice treated with ciprofloxacin (7.5 mg/kg or 15 mg/kg) had significant reductions in clinical signs, body weight loss, splenic and colonic weight increase compared with saline-treated and ceftazidime-treated mice. Histologic analysis showed mild inflammation in ciprofloxacin-treated mice with a mean score of 3.8 +/- 0.5 points compared with moderate colitis scored 7.8 +/- 1.3 and 9.5 +/- 0.5 points in saline and ceftazidime-treated mice, respectively. Analysis of cytokine levels in colon homogenates showed a significant decrease of IL-1beta, IL-8, and TNFalpha levels in ciprofloxacin-treated animals. Immunohistochemistry for NFkappaB showed strong positivity in saline and ceftazidime-treated mice in contrast to weak focal stain in ciprofloxacin- and dexamethasone-treated mice.


CONCLUSIONS
These findings imply that ciprofloxacin has an anti-inflammatory effect, rather than just an antibacterial one, making its use favorable in IBD patients.
Lahat
Guy
G
Department of Surgery, Sourasky Medical Center, Tel-Aviv, Israel.
Halperin
Drora
D
Barazovsky
Eli
E
Shalit
Itamar
I
Rabau
Micha
M
Klausner
Josef
J
Fabian
Ina
I
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use* / Q000633:toxicity; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use* / Q000633:toxicity; D002442:Ceftazidime / Q000627:therapeutic use / Q000633:toxicity; D002939:Ciprofloxacin / Q000627:therapeutic use* / Q000633:toxicity; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D007249:Inflammation; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D014302:Trinitrobenzenesulfonic Acid; D015431:Weight Loss / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D002939:Ciprofloxacin; D003907:Dexamethasone; D014302:Trinitrobenzenesulfonic Acid; D002442:Ceftazidime