Ciprofloxacin inhibits cytokine-induced nitric oxide production in human colonic epithelium.
BACKGROUND
The fluoroquinolone ciprofloxacin is a broad-spectrum antibiotic that has been used in the treatment of inflammatory bowel diseases. There is evidence that quinolones have immunomodulating activities via the regulation of cytokine production.


METHODS
We investigated the effect of ciprofloxacin on the nitric oxide (NO) production by colonic epithelium. HT-29 cells and colonic biopsies from patients (n = 4) with ulcerative colitis (UC) and normal controls (n = 4) were cultured with various concentrations of ciprofloxacin (10-100 microg mL(-1)) in the presence and absence of pro-inflammatory cytokines. The production of NO was measured in culture supernatants with a spectrophotometric method and inducible nitric oxide synthase (iNOS) mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Ciprofloxacin did not have any effect on the basal NO production by HT-29 cells. In contrast, ciprofloxacin significantly (P < 0.001) inhibited the pro-inflammatory cytokines (interleukin-1alpha + tumour necrosis factor-alpha + interferon-gamma)-induced NO production in HT-29, in a concentration-dependent manner, via the inhibition of the cytokine-induced iNOS mRNA expression. Wortmannin produced a concentration related reversal of the inhibitory effect of ciprofloxacin at both iNOS mRNA expression and NO production in HT-29 cells. A similar inhibitory effect of ciprofloxacin on the cytokine-induced NO production and iNOS mRNA expression was detected in vitro in cultures of normal colonic tissue. In addition, ciprofloxacin significantly inhibited the NO production and iNOS mRNA expression in cultures of colonic tissue from ulcerative colitis patients, in a concentration-dependent manner.


CONCLUSIONS
These data suggest that ciprofloxacin, in addition to its antimicrobial role, might have an immunoregulatory effect on intestinal inflammation, via the modulation of inflammatory mediators.
Kolios
G
G
Department of Gastroenterology, Faculty of Medicine, University of Crete, Heraklion, Greece. gkolios@med.uoc.gr
Manousou
P
P
Bourikas
L
L
Notas
G
G
Tsagarakis
N
N
Mouzas
I
I
Kouroumalis
E
E
D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D003106:Colon / Q000201:enzymology / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D009569:Nitric Oxide; D002939:Ciprofloxacin; D019001:Nitric Oxide Synthase