title: Norfloxacin modulates the inflammatory response and directly affects neutrophils in patients with decompensated cirrhosis.
abstract: OBJECTIVE
  Patients with cirrhosis undergoing selective intestinal decontamination with norfloxacin show a reduction in serum cytokine levels, probably because of a combined effect of norfloxacin on bowel flora and neutrophils.
  
  
  METHODS
  Thirty-one patients with cirrhosis receiving norfloxacin (400 mg/day) were included. Blood samples were collected at 0.5-4 hours (peak samples group, n = 47) and at 22-24 hours (trough samples group, n = 84) after dose. Fifty-nine ascitic fluid samples were obtained. Single doses of norfloxacin and trimethoprim/sulfamethoxazole were administered to 13 and 5 patients, respectively, (temporal profile group) and samples were collected at 0, 0.5, 1, 1.5, 2, 4, and 24 hours. Norfloxacin, trimethoprim/sulfamethoxazole, cytokines, nitric oxide, expression levels of nuclear factor (NF)-kappaB and inhibitor of NF-kappaB (IkB-alpha), neutrophil oxidative burst, and rate of apoptotic events were determined.
  
  
  RESULTS
  All samples were bacterial DNA negative and had no significant levels of lipopolysaccharide. Serum and ascitic levels of tumor necrosis factor-alpha, interferon-gamma, interleukin-12, and nitric oxide were significantly lower in peak than in trough samples. A correlation was present between serum norfloxacins concentrations and tumor necrosis factor-alpha (r = -0.68; P < .001), interferon-gamma (r = -0.66; P < .001), interleukin-12 (r = -0.66; P < .001), and nitric oxide (r = -0.68; P < .001). Serum norfloxacin's highest concentrations (1 +/- 0.5 microg/mL) were achieved at 1-2 hours and concurred in time with the lower levels of cytokines and nitric oxide. Intracellular norfloxacin's highest levels (2 +/- 1 microg/mL/10(7) cells) were observed at 2 hours and concurred with a lower NF-kappaB expression, a reduced anion superoxide generation, and apoptotic rate in response to phorbol myristate acetate. Trimethoprim/sulfamethoxazole did not significantly modulate cytokine expression.
  
  
  CONCLUSIONS
  Norfloxacin but not trimethoprim/sulfamethoxazole modulates inflammatory response and directly affects neutrophils in patients with cirrhosis.
authors: Sección de Farmacología Clínica, Hospital General Universitario, Alicante, and Universidad Miguel Hernández, Elche, Spain.
authors: Pedro
authors: P
authors: Zapater
authors: Rocío
authors: R
authors: Caño
authors: Lucía
authors: L
authors: Llanos
authors: Antonio J
authors: AJ
authors: Ruiz-Alcaraz
authors: Sonia
authors: S
authors: Pascual
authors: Claudia
authors: C
authors: Barquero
authors: Rocío
authors: R
authors: Moreu
authors: Pablo
authors: P
authors: Bellot
authors: José F
authors: JF
authors: Horga
authors: Carlos
authors: C
authors: Muñoz
authors: Jara
authors: J
authors: Pérez
authors: Pilar
authors: P
authors: García-Peñarrubia
authors: Miguel
authors: M
authors: Pérez-Mateo
authors: José
authors: J
authors: Such
authors: Rubén
authors: R
authors: Francés
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control; D015331:Cohort Studies; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009643:Norfloxacin / Q000494:pharmacology* / Q000627:therapeutic use; D010538:Peritonitis / Q000209:etiology / Q000517:prevention & control; D016897:Respiratory Burst / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D016328:NF-kappa B; D009643:Norfloxacin